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Long COVID appears to ‘impair’ survival in cancer patients
More than one in six cancer patients experience long-term sequelae following SARS-CoV-2 infection, placing them at increased risk of discontinuing their cancer treatment or dying, according to European registry data.
Given the “high lethality” of COVID-19 in cancer patients and the risk for long-term complications following infection in the general population, Alessio Cortellini, MD, a consultant medical oncologist at Hammersmith Hospital and Imperial College London, and colleagues wanted to explore the “prevalence and clinical significance of COVID-19 sequelae in cancer patients and their oncological continuity of care.”
Dr. Cortellini presented the OnCovid registry research on Sept. 21 at the 2021 European Society for Medical Oncology Congress. He reported that overall, the data suggest that post–COVID-19 complications may “impair” patients’ cancer survival as well as their cancer care.
The OnCovid registry data showed that the 15% of cancer patients who had long-term COVID-19 complications were 76% more likely to die than those without sequelae. Cancer patients with COVID-19 sequelae were significantly more likely to permanently stop taking their systemic anticancer therapy, and they were more than 3.5 times more likely to die than those who continued their treatment as planned. In terms of long-term complications, almost half of patients experienced dyspnea, and two-fifths reported chronic fatigue.
“This data confirms the need to continue to prioritize cancer patients,” Antonio Passaro, MD, PhD, division of thoracic oncology, European Institute of Oncology IRCCS, Milan, commented in a press release. “In the fight against the pandemic, it is of the utmost importance that we do not neglect to study and understand the curves of cancer incidence and mortality.”
Invited to discuss the results, Anne-Marie C. Dingemans, MD, PhD, a pulmonologist and professor of thoracic oncology at Erasmus Medical Center, Rotterdam, the Netherlands, said COVID-19 remains a “very important” issue for cancer patients.
Interestingly, Dr. Dingemans noted that COVID-19 sequelae in patients with cancer appear to occur slightly less frequently, compared with estimates in the general population – which range from 13% to 60% – though patients with cancer tend to have more respiratory problems.
However, Dr. Dingemans added, the difficulty with comparing sequelae rates between cancer patients and the general population is that cancer patients “probably already have a lot of symptoms” associated with long COVID, such as dyspnea and fatigue, and may not be aware that they are experiencing COVID sequelae.
The registry results
To investigate the long-term impact of COVID-19 on survival and continuity of care, the team examined data from the OnCovid registry, which was established at the beginning of the pandemic to study consecutive patients aged 18 years and older with confirmed SARS-CoV-2 infection and a history of solid or hematologic malignancies.
At the data cutoff on March 1, 2021, the registry included 35 institutions in six European countries. The institutions collected information on patient demographics and comorbidities, cancer history, anticancer therapy, COVID-19 investigations, and COVID-19–specific therapies.
For the current analysis, the team included 1,557 of 2,634 patients who had undergone a clinical reassessment after recovering from COVID-19. Information sufficient to conduct multivariate analysis was available for 840 of these patients.
About half of the patients were younger than 60 years, and just over half were women. The most common cancer diagnoses were breast cancer (23.4%), gastrointestinal tumors (16.5%), gynecologic/genitourinary tumors (19.3%), and hematologic cancers (14.1%), with even distribution between local/locoregional and advanced disease.
The median interval between COVID-19 recovery and reassessment was 44 days, and the mean post–COVID-19 follow-up period was 128 days.
About 15% of patients experienced at least one long-term sequela from COVID-19. The most common were dyspnea/shortness of breath (49.6%), fatigue (41.0%), chronic cough (33.8%), and other respiratory complications (10.7%).
Dr. Cortellini noted that cancer patients who experienced sequelae were more likely to be male, aged 65 years or older, to have at least two comorbidities, and to have a history of smoking. In addition, cancer patients who experienced long-term complications were significantly more likely to have had COVID-19 complications, to have required COVID-19 therapy, and to have been hospitalized for the disease.
Factoring in gender, age, comorbidity burden, primary tumor, stage, receipt of anticancer and anti–COVID-19 therapy, COVID-19 complications, and hospitalization, the team found that COVID-19 sequelae were independently associated with an increased risk for death (hazard ratio, 1.76).
Further analysis of patterns of systemic anticancer therapy in 471 patients revealed that 14.8% of COVID-19 survivors permanently discontinued therapy and that a dose or regimen adjustment occurred for 37.8%.
Patients who permanently discontinued anticancer therapy were more likely to be former or current smokers, to have had COVID-19 complications or been hospitalized for COVID-19, and to have had COVID-19 sequelae at reassessment. The investigators found no association between permanent discontinuation of therapy and cancer disease stage.
Dr. Cortellini and colleagues reported that permanent cessation of systemic anticancer therapy was associated with an increased risk for death. A change in dose or regimen did not affect survival.
The most common reason for stopping therapy permanently was deterioration of the patient’s performance status (61.3%), followed by disease progression (29.0%). Dose or regimen adjustments typically occurred to avoid immune suppression (50.0%), hospitalization (25.8%), and intravenous drug administration (19.1%).
Dr. Cortellini concluded his presentation by highlighting the importance of increasing awareness of long COVID in patients with cancer as well as early treatment of COVID-19 sequelae to improve patient outcomes.
The study was funded by the Imperial College Biomedical Research Center. Dr. Cortellini has relationships with MSD, Bristol-Myers Squibb, Roche, Novartis, AstraZeneca, Astellas, and Sun Pharma. Dr. Dingemans has relationships with Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Jansen, Chiesi, Amgen, Pfizer, Bayer, Takeda, Pharmamar, and Sanofi.
A version of this article first appeared on Medscape.com.
More than one in six cancer patients experience long-term sequelae following SARS-CoV-2 infection, placing them at increased risk of discontinuing their cancer treatment or dying, according to European registry data.
Given the “high lethality” of COVID-19 in cancer patients and the risk for long-term complications following infection in the general population, Alessio Cortellini, MD, a consultant medical oncologist at Hammersmith Hospital and Imperial College London, and colleagues wanted to explore the “prevalence and clinical significance of COVID-19 sequelae in cancer patients and their oncological continuity of care.”
Dr. Cortellini presented the OnCovid registry research on Sept. 21 at the 2021 European Society for Medical Oncology Congress. He reported that overall, the data suggest that post–COVID-19 complications may “impair” patients’ cancer survival as well as their cancer care.
The OnCovid registry data showed that the 15% of cancer patients who had long-term COVID-19 complications were 76% more likely to die than those without sequelae. Cancer patients with COVID-19 sequelae were significantly more likely to permanently stop taking their systemic anticancer therapy, and they were more than 3.5 times more likely to die than those who continued their treatment as planned. In terms of long-term complications, almost half of patients experienced dyspnea, and two-fifths reported chronic fatigue.
“This data confirms the need to continue to prioritize cancer patients,” Antonio Passaro, MD, PhD, division of thoracic oncology, European Institute of Oncology IRCCS, Milan, commented in a press release. “In the fight against the pandemic, it is of the utmost importance that we do not neglect to study and understand the curves of cancer incidence and mortality.”
Invited to discuss the results, Anne-Marie C. Dingemans, MD, PhD, a pulmonologist and professor of thoracic oncology at Erasmus Medical Center, Rotterdam, the Netherlands, said COVID-19 remains a “very important” issue for cancer patients.
Interestingly, Dr. Dingemans noted that COVID-19 sequelae in patients with cancer appear to occur slightly less frequently, compared with estimates in the general population – which range from 13% to 60% – though patients with cancer tend to have more respiratory problems.
However, Dr. Dingemans added, the difficulty with comparing sequelae rates between cancer patients and the general population is that cancer patients “probably already have a lot of symptoms” associated with long COVID, such as dyspnea and fatigue, and may not be aware that they are experiencing COVID sequelae.
The registry results
To investigate the long-term impact of COVID-19 on survival and continuity of care, the team examined data from the OnCovid registry, which was established at the beginning of the pandemic to study consecutive patients aged 18 years and older with confirmed SARS-CoV-2 infection and a history of solid or hematologic malignancies.
At the data cutoff on March 1, 2021, the registry included 35 institutions in six European countries. The institutions collected information on patient demographics and comorbidities, cancer history, anticancer therapy, COVID-19 investigations, and COVID-19–specific therapies.
For the current analysis, the team included 1,557 of 2,634 patients who had undergone a clinical reassessment after recovering from COVID-19. Information sufficient to conduct multivariate analysis was available for 840 of these patients.
About half of the patients were younger than 60 years, and just over half were women. The most common cancer diagnoses were breast cancer (23.4%), gastrointestinal tumors (16.5%), gynecologic/genitourinary tumors (19.3%), and hematologic cancers (14.1%), with even distribution between local/locoregional and advanced disease.
The median interval between COVID-19 recovery and reassessment was 44 days, and the mean post–COVID-19 follow-up period was 128 days.
About 15% of patients experienced at least one long-term sequela from COVID-19. The most common were dyspnea/shortness of breath (49.6%), fatigue (41.0%), chronic cough (33.8%), and other respiratory complications (10.7%).
Dr. Cortellini noted that cancer patients who experienced sequelae were more likely to be male, aged 65 years or older, to have at least two comorbidities, and to have a history of smoking. In addition, cancer patients who experienced long-term complications were significantly more likely to have had COVID-19 complications, to have required COVID-19 therapy, and to have been hospitalized for the disease.
Factoring in gender, age, comorbidity burden, primary tumor, stage, receipt of anticancer and anti–COVID-19 therapy, COVID-19 complications, and hospitalization, the team found that COVID-19 sequelae were independently associated with an increased risk for death (hazard ratio, 1.76).
Further analysis of patterns of systemic anticancer therapy in 471 patients revealed that 14.8% of COVID-19 survivors permanently discontinued therapy and that a dose or regimen adjustment occurred for 37.8%.
Patients who permanently discontinued anticancer therapy were more likely to be former or current smokers, to have had COVID-19 complications or been hospitalized for COVID-19, and to have had COVID-19 sequelae at reassessment. The investigators found no association between permanent discontinuation of therapy and cancer disease stage.
Dr. Cortellini and colleagues reported that permanent cessation of systemic anticancer therapy was associated with an increased risk for death. A change in dose or regimen did not affect survival.
The most common reason for stopping therapy permanently was deterioration of the patient’s performance status (61.3%), followed by disease progression (29.0%). Dose or regimen adjustments typically occurred to avoid immune suppression (50.0%), hospitalization (25.8%), and intravenous drug administration (19.1%).
Dr. Cortellini concluded his presentation by highlighting the importance of increasing awareness of long COVID in patients with cancer as well as early treatment of COVID-19 sequelae to improve patient outcomes.
The study was funded by the Imperial College Biomedical Research Center. Dr. Cortellini has relationships with MSD, Bristol-Myers Squibb, Roche, Novartis, AstraZeneca, Astellas, and Sun Pharma. Dr. Dingemans has relationships with Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Jansen, Chiesi, Amgen, Pfizer, Bayer, Takeda, Pharmamar, and Sanofi.
A version of this article first appeared on Medscape.com.
More than one in six cancer patients experience long-term sequelae following SARS-CoV-2 infection, placing them at increased risk of discontinuing their cancer treatment or dying, according to European registry data.
Given the “high lethality” of COVID-19 in cancer patients and the risk for long-term complications following infection in the general population, Alessio Cortellini, MD, a consultant medical oncologist at Hammersmith Hospital and Imperial College London, and colleagues wanted to explore the “prevalence and clinical significance of COVID-19 sequelae in cancer patients and their oncological continuity of care.”
Dr. Cortellini presented the OnCovid registry research on Sept. 21 at the 2021 European Society for Medical Oncology Congress. He reported that overall, the data suggest that post–COVID-19 complications may “impair” patients’ cancer survival as well as their cancer care.
The OnCovid registry data showed that the 15% of cancer patients who had long-term COVID-19 complications were 76% more likely to die than those without sequelae. Cancer patients with COVID-19 sequelae were significantly more likely to permanently stop taking their systemic anticancer therapy, and they were more than 3.5 times more likely to die than those who continued their treatment as planned. In terms of long-term complications, almost half of patients experienced dyspnea, and two-fifths reported chronic fatigue.
“This data confirms the need to continue to prioritize cancer patients,” Antonio Passaro, MD, PhD, division of thoracic oncology, European Institute of Oncology IRCCS, Milan, commented in a press release. “In the fight against the pandemic, it is of the utmost importance that we do not neglect to study and understand the curves of cancer incidence and mortality.”
Invited to discuss the results, Anne-Marie C. Dingemans, MD, PhD, a pulmonologist and professor of thoracic oncology at Erasmus Medical Center, Rotterdam, the Netherlands, said COVID-19 remains a “very important” issue for cancer patients.
Interestingly, Dr. Dingemans noted that COVID-19 sequelae in patients with cancer appear to occur slightly less frequently, compared with estimates in the general population – which range from 13% to 60% – though patients with cancer tend to have more respiratory problems.
However, Dr. Dingemans added, the difficulty with comparing sequelae rates between cancer patients and the general population is that cancer patients “probably already have a lot of symptoms” associated with long COVID, such as dyspnea and fatigue, and may not be aware that they are experiencing COVID sequelae.
The registry results
To investigate the long-term impact of COVID-19 on survival and continuity of care, the team examined data from the OnCovid registry, which was established at the beginning of the pandemic to study consecutive patients aged 18 years and older with confirmed SARS-CoV-2 infection and a history of solid or hematologic malignancies.
At the data cutoff on March 1, 2021, the registry included 35 institutions in six European countries. The institutions collected information on patient demographics and comorbidities, cancer history, anticancer therapy, COVID-19 investigations, and COVID-19–specific therapies.
For the current analysis, the team included 1,557 of 2,634 patients who had undergone a clinical reassessment after recovering from COVID-19. Information sufficient to conduct multivariate analysis was available for 840 of these patients.
About half of the patients were younger than 60 years, and just over half were women. The most common cancer diagnoses were breast cancer (23.4%), gastrointestinal tumors (16.5%), gynecologic/genitourinary tumors (19.3%), and hematologic cancers (14.1%), with even distribution between local/locoregional and advanced disease.
The median interval between COVID-19 recovery and reassessment was 44 days, and the mean post–COVID-19 follow-up period was 128 days.
About 15% of patients experienced at least one long-term sequela from COVID-19. The most common were dyspnea/shortness of breath (49.6%), fatigue (41.0%), chronic cough (33.8%), and other respiratory complications (10.7%).
Dr. Cortellini noted that cancer patients who experienced sequelae were more likely to be male, aged 65 years or older, to have at least two comorbidities, and to have a history of smoking. In addition, cancer patients who experienced long-term complications were significantly more likely to have had COVID-19 complications, to have required COVID-19 therapy, and to have been hospitalized for the disease.
Factoring in gender, age, comorbidity burden, primary tumor, stage, receipt of anticancer and anti–COVID-19 therapy, COVID-19 complications, and hospitalization, the team found that COVID-19 sequelae were independently associated with an increased risk for death (hazard ratio, 1.76).
Further analysis of patterns of systemic anticancer therapy in 471 patients revealed that 14.8% of COVID-19 survivors permanently discontinued therapy and that a dose or regimen adjustment occurred for 37.8%.
Patients who permanently discontinued anticancer therapy were more likely to be former or current smokers, to have had COVID-19 complications or been hospitalized for COVID-19, and to have had COVID-19 sequelae at reassessment. The investigators found no association between permanent discontinuation of therapy and cancer disease stage.
Dr. Cortellini and colleagues reported that permanent cessation of systemic anticancer therapy was associated with an increased risk for death. A change in dose or regimen did not affect survival.
The most common reason for stopping therapy permanently was deterioration of the patient’s performance status (61.3%), followed by disease progression (29.0%). Dose or regimen adjustments typically occurred to avoid immune suppression (50.0%), hospitalization (25.8%), and intravenous drug administration (19.1%).
Dr. Cortellini concluded his presentation by highlighting the importance of increasing awareness of long COVID in patients with cancer as well as early treatment of COVID-19 sequelae to improve patient outcomes.
The study was funded by the Imperial College Biomedical Research Center. Dr. Cortellini has relationships with MSD, Bristol-Myers Squibb, Roche, Novartis, AstraZeneca, Astellas, and Sun Pharma. Dr. Dingemans has relationships with Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Jansen, Chiesi, Amgen, Pfizer, Bayer, Takeda, Pharmamar, and Sanofi.
A version of this article first appeared on Medscape.com.
Nivo/ipi combo now ‘standard of care’ in mesothelioma
After 3 years, 23% of patients who received combination immunotherapy were still alive, in comparison with 15% of patients in the chemotherapy arm.
Combination immunotherapy continued to provide a “durable and long-term benefit” compared with chemotherapy, commented Solange Peters, MD, from the Oncology Department, Center Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The new data from the additional 12 months of follow-up “confirm nivolumab plus ipilimumab as a standard of care for unresectable MPM, regardless of histology,” she commented.
She presented the update on September 17 at the annual meeting of the European Society of Medical Oncology (ESMO). She is the current president of the organization.
Previously, 2-year data from this study showed that the combination yielded a median overall survival of 18.1 months, compared to 14.1 months with standard-of-care chemotherapy.
As reported by this news organization, this translated into a 26% improvement in overall survival; 41% of patients in the immunotherapy arm were still alive at 2 years, versus 27% in the chemotherapy group.
On the basis of these data, the combination was subsequently approved in the United States, the European Union, and elsewhere for the first-line treatment of adults with unresectable MPM.
The new data come from a 3-year update, as well as an exploratory biomarker analysis. The new data show significantly improved overall survival with the combination immunotherapy. Among those who responded to immunotherapy, response was ongoing for 28% of patients at 3 years.
Benefit was seen even for patients who discontinued the treatment because of treatment-related adverse events, indicating that discontinuance does not appear to have a negative impact on the long-term benefits, Dr. Peters commented.
In addition, the new analysis suggested that patients with a high score on a four-gene inflammatory signature did particularly well with nivolumab plus ipilimumab, whereas chemotherapy patients did worse if they had nonepithelioid disease, a finding not seen with immunotherapy.
The discussant for this abstract, Pilar Garrido, MD, PhD, associate professor of medicine at the Universidad de Alcalá, Madrid, said that despite the impressive findings, there is a “critical need” to establish predictive biomarkers in MPM.
This is particularly pressing in cases involving early progression, inasmuch as median progression-free survival (PFS) in CheckMate 743 was similar overall, and chemotherapy performed better than immunotherapy in the first 8 months.
There is also a need to be able to identify patients who will have an ongoing response at 3 years, as well as to clarify the impact of toxicity, given that the median duration of response was 20 months following discontinuation of treatment after just 4 months.
Dr. Garrido cautioned that the exploratory analyses were of “limited value,” because RNA data for the gene signature analysis were available for only 54% of patients, and the study was not powered to detect differences on the basis of programmed cell death–ligand-1 (PD-L1) expression.
Summarizing, Dr. Garrido said that although the current results showed that combination immunotherapy “continued to provide” a survival benefit in “a subgroup of patients,” the “better characterization of predictive biomarkers” will be “crucial” to improving these results.
Study details
Dr. Peters reminded the audience that the CheckMate 743 trial involved patients with unresectable MPM who had not previously received any systemic therapy and who had a good performance status.
A total of 605 patients were enrolled. They were randomly assigned in a 1:1 ratio to receive either nivolumab plus ipilimumab for up to 2 years or six cycles of pemetrexed plus cisplatin or carboplatin.
The median age of the patients was 69 years, and 77% were men. The baseline characteristics were well balanced between the two treatment groups; 75% to 76% had epithelioid disease, and for 74% to 80% of patients, baseline PD-L1 expression was greater than or equal to 1%.
Subgroup analysis indicated that combination immunotherapy was beneficial regardless of patient age, sex, performance status, and smoking status.
However, the new analysis suggested that the improvement in overall survival depended on PD-L1 expression, at a hazard ratio for combination immunotherapy versus chemotherapy of 0.71 in patients with expression of greater than or equal to 1%, compared with 0.99 for patients with expression of less than 1%.
Dr. Peters explained that the performance of nivolumab plus ipilimumab was identical in both PD-L1 expression groups, but it was the chemotherapy arm that performed markedly better for patients with expression of less than 1%.
An inverse finding was observed when patients were stratified by tumor histology.
In those with epithelioid disease, the median overall survival with combination immunotherapy was 18.2 months, versus 16.7 with chemotherapy, at a hazard ratio of 0.85.
At 36 months, 24% of immunotherapy patients were still alive, as were 19% of those given standard-of-care chemotherapy.
Among patients with nonepithelioid disease, however, median overall survival was 18.1 months with nivolumab plus ipilimumab, versus just 8.8 months with chemotherapy, at a hazard ratio of 0.48. At 3 years, 22% of patients who received combination immunotherapy were still alive, compared with 4% of those who received chemotherapy.
Other results showed that PFS was only slightly longer with combination immunotherapy, at 6.8 months versus 7.2 months, for a hazard ratio of 0.92.
Yet at 36 months, 14% of patients who received nivolumab plus ipilimumab had not experienced disease progression, versus just 1% of those in the chemotherapy arm.
This difference was even more pronounced when the researchers assessed objective response rates: 28% of patients who received combination immunotherapy were still responding at 36 months, versus 0% among patients given chemotherapy.
This translated into a median duration of response of 11.6 months for nivolumab plus ipilimumab, versus 6.7 months with chemotherapy.
The safety assessment showed that rates of treatment-related adverse events of any grade and of grade 3-4 were similar between the combination immunotherapy and chemotherapy arms.
However, rates of treatment-related adverse events that led to discontinuation of all components of the regimen were higher with immunotherapy, at 17% for events of any grade and 13% for events of grade 3-4, compared with 8% and 5%, respectively, with chemotherapy.
Serious treatment-related adverse events were more common with nivolumab plus ipilimumab. Events of grade 3-4 occurred in 13% of patients with nivolumab plus ipilimumab, versus 5% with chemotherapy.
Dr. Peters showed that this did not severely affect overall survival, however. Among patients who discontinued combination immunotherapy, the median duration of response was 20.0 months.
Median overall survival in these patients was 25.4 months, and the 3-year overall survival rate was 37%.
The study was funded by Bristol-Myers Squibb. Dr. Peters and Dr. Garrido reported relationships with numerous sources in industry.
A version of this article first appeared on Medscape.com.
After 3 years, 23% of patients who received combination immunotherapy were still alive, in comparison with 15% of patients in the chemotherapy arm.
Combination immunotherapy continued to provide a “durable and long-term benefit” compared with chemotherapy, commented Solange Peters, MD, from the Oncology Department, Center Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The new data from the additional 12 months of follow-up “confirm nivolumab plus ipilimumab as a standard of care for unresectable MPM, regardless of histology,” she commented.
She presented the update on September 17 at the annual meeting of the European Society of Medical Oncology (ESMO). She is the current president of the organization.
Previously, 2-year data from this study showed that the combination yielded a median overall survival of 18.1 months, compared to 14.1 months with standard-of-care chemotherapy.
As reported by this news organization, this translated into a 26% improvement in overall survival; 41% of patients in the immunotherapy arm were still alive at 2 years, versus 27% in the chemotherapy group.
On the basis of these data, the combination was subsequently approved in the United States, the European Union, and elsewhere for the first-line treatment of adults with unresectable MPM.
The new data come from a 3-year update, as well as an exploratory biomarker analysis. The new data show significantly improved overall survival with the combination immunotherapy. Among those who responded to immunotherapy, response was ongoing for 28% of patients at 3 years.
Benefit was seen even for patients who discontinued the treatment because of treatment-related adverse events, indicating that discontinuance does not appear to have a negative impact on the long-term benefits, Dr. Peters commented.
In addition, the new analysis suggested that patients with a high score on a four-gene inflammatory signature did particularly well with nivolumab plus ipilimumab, whereas chemotherapy patients did worse if they had nonepithelioid disease, a finding not seen with immunotherapy.
The discussant for this abstract, Pilar Garrido, MD, PhD, associate professor of medicine at the Universidad de Alcalá, Madrid, said that despite the impressive findings, there is a “critical need” to establish predictive biomarkers in MPM.
This is particularly pressing in cases involving early progression, inasmuch as median progression-free survival (PFS) in CheckMate 743 was similar overall, and chemotherapy performed better than immunotherapy in the first 8 months.
There is also a need to be able to identify patients who will have an ongoing response at 3 years, as well as to clarify the impact of toxicity, given that the median duration of response was 20 months following discontinuation of treatment after just 4 months.
Dr. Garrido cautioned that the exploratory analyses were of “limited value,” because RNA data for the gene signature analysis were available for only 54% of patients, and the study was not powered to detect differences on the basis of programmed cell death–ligand-1 (PD-L1) expression.
Summarizing, Dr. Garrido said that although the current results showed that combination immunotherapy “continued to provide” a survival benefit in “a subgroup of patients,” the “better characterization of predictive biomarkers” will be “crucial” to improving these results.
Study details
Dr. Peters reminded the audience that the CheckMate 743 trial involved patients with unresectable MPM who had not previously received any systemic therapy and who had a good performance status.
A total of 605 patients were enrolled. They were randomly assigned in a 1:1 ratio to receive either nivolumab plus ipilimumab for up to 2 years or six cycles of pemetrexed plus cisplatin or carboplatin.
The median age of the patients was 69 years, and 77% were men. The baseline characteristics were well balanced between the two treatment groups; 75% to 76% had epithelioid disease, and for 74% to 80% of patients, baseline PD-L1 expression was greater than or equal to 1%.
Subgroup analysis indicated that combination immunotherapy was beneficial regardless of patient age, sex, performance status, and smoking status.
However, the new analysis suggested that the improvement in overall survival depended on PD-L1 expression, at a hazard ratio for combination immunotherapy versus chemotherapy of 0.71 in patients with expression of greater than or equal to 1%, compared with 0.99 for patients with expression of less than 1%.
Dr. Peters explained that the performance of nivolumab plus ipilimumab was identical in both PD-L1 expression groups, but it was the chemotherapy arm that performed markedly better for patients with expression of less than 1%.
An inverse finding was observed when patients were stratified by tumor histology.
In those with epithelioid disease, the median overall survival with combination immunotherapy was 18.2 months, versus 16.7 with chemotherapy, at a hazard ratio of 0.85.
At 36 months, 24% of immunotherapy patients were still alive, as were 19% of those given standard-of-care chemotherapy.
Among patients with nonepithelioid disease, however, median overall survival was 18.1 months with nivolumab plus ipilimumab, versus just 8.8 months with chemotherapy, at a hazard ratio of 0.48. At 3 years, 22% of patients who received combination immunotherapy were still alive, compared with 4% of those who received chemotherapy.
Other results showed that PFS was only slightly longer with combination immunotherapy, at 6.8 months versus 7.2 months, for a hazard ratio of 0.92.
Yet at 36 months, 14% of patients who received nivolumab plus ipilimumab had not experienced disease progression, versus just 1% of those in the chemotherapy arm.
This difference was even more pronounced when the researchers assessed objective response rates: 28% of patients who received combination immunotherapy were still responding at 36 months, versus 0% among patients given chemotherapy.
This translated into a median duration of response of 11.6 months for nivolumab plus ipilimumab, versus 6.7 months with chemotherapy.
The safety assessment showed that rates of treatment-related adverse events of any grade and of grade 3-4 were similar between the combination immunotherapy and chemotherapy arms.
However, rates of treatment-related adverse events that led to discontinuation of all components of the regimen were higher with immunotherapy, at 17% for events of any grade and 13% for events of grade 3-4, compared with 8% and 5%, respectively, with chemotherapy.
Serious treatment-related adverse events were more common with nivolumab plus ipilimumab. Events of grade 3-4 occurred in 13% of patients with nivolumab plus ipilimumab, versus 5% with chemotherapy.
Dr. Peters showed that this did not severely affect overall survival, however. Among patients who discontinued combination immunotherapy, the median duration of response was 20.0 months.
Median overall survival in these patients was 25.4 months, and the 3-year overall survival rate was 37%.
The study was funded by Bristol-Myers Squibb. Dr. Peters and Dr. Garrido reported relationships with numerous sources in industry.
A version of this article first appeared on Medscape.com.
After 3 years, 23% of patients who received combination immunotherapy were still alive, in comparison with 15% of patients in the chemotherapy arm.
Combination immunotherapy continued to provide a “durable and long-term benefit” compared with chemotherapy, commented Solange Peters, MD, from the Oncology Department, Center Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The new data from the additional 12 months of follow-up “confirm nivolumab plus ipilimumab as a standard of care for unresectable MPM, regardless of histology,” she commented.
She presented the update on September 17 at the annual meeting of the European Society of Medical Oncology (ESMO). She is the current president of the organization.
Previously, 2-year data from this study showed that the combination yielded a median overall survival of 18.1 months, compared to 14.1 months with standard-of-care chemotherapy.
As reported by this news organization, this translated into a 26% improvement in overall survival; 41% of patients in the immunotherapy arm were still alive at 2 years, versus 27% in the chemotherapy group.
On the basis of these data, the combination was subsequently approved in the United States, the European Union, and elsewhere for the first-line treatment of adults with unresectable MPM.
The new data come from a 3-year update, as well as an exploratory biomarker analysis. The new data show significantly improved overall survival with the combination immunotherapy. Among those who responded to immunotherapy, response was ongoing for 28% of patients at 3 years.
Benefit was seen even for patients who discontinued the treatment because of treatment-related adverse events, indicating that discontinuance does not appear to have a negative impact on the long-term benefits, Dr. Peters commented.
In addition, the new analysis suggested that patients with a high score on a four-gene inflammatory signature did particularly well with nivolumab plus ipilimumab, whereas chemotherapy patients did worse if they had nonepithelioid disease, a finding not seen with immunotherapy.
The discussant for this abstract, Pilar Garrido, MD, PhD, associate professor of medicine at the Universidad de Alcalá, Madrid, said that despite the impressive findings, there is a “critical need” to establish predictive biomarkers in MPM.
This is particularly pressing in cases involving early progression, inasmuch as median progression-free survival (PFS) in CheckMate 743 was similar overall, and chemotherapy performed better than immunotherapy in the first 8 months.
There is also a need to be able to identify patients who will have an ongoing response at 3 years, as well as to clarify the impact of toxicity, given that the median duration of response was 20 months following discontinuation of treatment after just 4 months.
Dr. Garrido cautioned that the exploratory analyses were of “limited value,” because RNA data for the gene signature analysis were available for only 54% of patients, and the study was not powered to detect differences on the basis of programmed cell death–ligand-1 (PD-L1) expression.
Summarizing, Dr. Garrido said that although the current results showed that combination immunotherapy “continued to provide” a survival benefit in “a subgroup of patients,” the “better characterization of predictive biomarkers” will be “crucial” to improving these results.
Study details
Dr. Peters reminded the audience that the CheckMate 743 trial involved patients with unresectable MPM who had not previously received any systemic therapy and who had a good performance status.
A total of 605 patients were enrolled. They were randomly assigned in a 1:1 ratio to receive either nivolumab plus ipilimumab for up to 2 years or six cycles of pemetrexed plus cisplatin or carboplatin.
The median age of the patients was 69 years, and 77% were men. The baseline characteristics were well balanced between the two treatment groups; 75% to 76% had epithelioid disease, and for 74% to 80% of patients, baseline PD-L1 expression was greater than or equal to 1%.
Subgroup analysis indicated that combination immunotherapy was beneficial regardless of patient age, sex, performance status, and smoking status.
However, the new analysis suggested that the improvement in overall survival depended on PD-L1 expression, at a hazard ratio for combination immunotherapy versus chemotherapy of 0.71 in patients with expression of greater than or equal to 1%, compared with 0.99 for patients with expression of less than 1%.
Dr. Peters explained that the performance of nivolumab plus ipilimumab was identical in both PD-L1 expression groups, but it was the chemotherapy arm that performed markedly better for patients with expression of less than 1%.
An inverse finding was observed when patients were stratified by tumor histology.
In those with epithelioid disease, the median overall survival with combination immunotherapy was 18.2 months, versus 16.7 with chemotherapy, at a hazard ratio of 0.85.
At 36 months, 24% of immunotherapy patients were still alive, as were 19% of those given standard-of-care chemotherapy.
Among patients with nonepithelioid disease, however, median overall survival was 18.1 months with nivolumab plus ipilimumab, versus just 8.8 months with chemotherapy, at a hazard ratio of 0.48. At 3 years, 22% of patients who received combination immunotherapy were still alive, compared with 4% of those who received chemotherapy.
Other results showed that PFS was only slightly longer with combination immunotherapy, at 6.8 months versus 7.2 months, for a hazard ratio of 0.92.
Yet at 36 months, 14% of patients who received nivolumab plus ipilimumab had not experienced disease progression, versus just 1% of those in the chemotherapy arm.
This difference was even more pronounced when the researchers assessed objective response rates: 28% of patients who received combination immunotherapy were still responding at 36 months, versus 0% among patients given chemotherapy.
This translated into a median duration of response of 11.6 months for nivolumab plus ipilimumab, versus 6.7 months with chemotherapy.
The safety assessment showed that rates of treatment-related adverse events of any grade and of grade 3-4 were similar between the combination immunotherapy and chemotherapy arms.
However, rates of treatment-related adverse events that led to discontinuation of all components of the regimen were higher with immunotherapy, at 17% for events of any grade and 13% for events of grade 3-4, compared with 8% and 5%, respectively, with chemotherapy.
Serious treatment-related adverse events were more common with nivolumab plus ipilimumab. Events of grade 3-4 occurred in 13% of patients with nivolumab plus ipilimumab, versus 5% with chemotherapy.
Dr. Peters showed that this did not severely affect overall survival, however. Among patients who discontinued combination immunotherapy, the median duration of response was 20.0 months.
Median overall survival in these patients was 25.4 months, and the 3-year overall survival rate was 37%.
The study was funded by Bristol-Myers Squibb. Dr. Peters and Dr. Garrido reported relationships with numerous sources in industry.
A version of this article first appeared on Medscape.com.
Adjuvant pembro success in early melanoma raises questions
However, the results raise many questions, says an expert invited to discuss the new data.
Adjuvant pembrolizumab is already approved in the United States for use in patients with melanoma with lymph node involvement following complete resection, having been shown to prolong both recurrence-free and distant metastasis-free survival (DMFS) in stage 3 melanoma.
This latest trial involved patients with slightly earlier disease, those with resected stage 2B and 2C melanoma. These patients are at “high risk” of disease recurrence and have similar outcomes to stage 3A and 3B melanoma patients, explained study presenter Jason J. Luke, MD, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, Pittsburgh.
Results from the KEYNOTE-716 trial showed that adjuvant pembrolizumab is also beneficial in this earlier stage disease: it improved recurrence-free survival (RFS) by 35% and improved distant metastasis-free survival by 40% compared with placebo.
Adjuvant pembrolizumab is an “effective treatment option with a favorable benefit-risk profile for patients with high-risk stage 2 melanoma,” Dr. Luke concluded.
The manufacturer, Merck, has said that these new results have already been accepted for priority review by the U.S. Food and Drug Administration, making it likely that the indication will be extended to include patients with earlier disease.
Dr. Luke presented the results at the European Society of Medical Oncology 2021 annual meeting.
Invited discussant Omid Hamid, MD, chief of research/immuno-oncology, the Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, said that Dr. Luke’s presentation was “amazing.”
However, these new results have “sabotaged how we think about how we treat our patients and how we’re going to think about what we do in the future.”
Dr. Hamid noted that the incidence of stage 2B and 2C melanoma is “equal” to that of stage 3 disease, “so with a proposed approval” of pembrolizumab in this earlier setting, “we will have a lot more patients” to treat earlier in their disease course.
Of course, this raises the inevitable question of how to treat these patients when they relapse, and how to treat these patients in the metastatic setting “having already exhausted single-agent PD-1 therapy,” he commented.
Dr. Hamid said that the current results also reveal the “current problem” with adjuvant therapy, which is that “we don’t know who benefits,” and there is a subset patients who “never recur” even if they are untreated.
So the questions are: “How come all get treated? What about the risks of toxicity? The costs? And where do we fit these patients into clinic?”
As with so many presentations of immunotherapy trial data, the need for biomarkers was raised, with Dr. Hamid emphasizing the need for predictive biomarkers that could exclude patients, and save them from toxicity.
He noted that there were data with another checkpoint inhibitor, nivolumab (Opdivo), in the adjuvant setting (from the CheckMate 238 trial) that suggested higher tumor mutation burden and tumor interferon-gamma levels could play a role, and he hopes that similar data may be available from this latest trial.
Also, there are ongoing and upcoming trials in patients with stage 2B and 2C melanoma that may answer some of the outstanding questions, including a study of neoadjuvant PD-1 blockade before resection, and the DETECTION trial, which is exploring circulating tumor DNA-guided therapy postsurgery.
Then there is the NivoMela trial that will look at nivolumab in stage 2A as well as 2B and 2C disease, while the REFINE trial will assess whether giving immunotherapy less often to patients with advanced cancer, including those with melanoma, results in fewer side effects while continuing to be effective.
The current results also raise the question of whether to go “earlier and earlier” with adjuvant immunotherapy into “poor risk” stage 1 melanoma, which is already being tried in the United States, although there is “no clear understanding of what to do for those patients.”
Overall, Dr. Hamid said that the results of KEYNOTE-716 have “created more questions than answers,” including its impact on the inclusion criteria for phase 3/4 clinical trials, “which now exclude patients who have received adjuvant therapy within 6 months.”
“That will have to change,” he suggested.
Some of the questions raised by Dr. Hamid were discussed on social media, sparking a lively Twitter debate on how best to take the results forward and into the clinic.
Florentia Dimitriou, MD, a dermatology consultant in the Skin Cancer Clinic, University Hospital Zurich, Switzerland, said the data were “great” but she was “still unclear” over who needs adjuvant immunotherapy in this setting.
She also emphasized that, for her, the greater RFS benefit seen in T3b than in T4b disease “doesn’t make sense,” and she also highlighted the finding of long-term toxicity in approximately 18% of patients.
Dr. Luke replied that he agrees that the T3b/T4b results are puzzling but he said the event rate was “low” and the data are “immature,” and that he hopes to have “more info soon.”
He acknowledged that around 18% of patients taking pembrolizumab went on to receive hormone therapy for adverse events, including 13.9% due to hypothyroidism, and others including hypophysitis, adrenal sufficiency, and type 1 diabetes. However, he also pointed out that about 5% of patients in this study had background thyroid issues. The risks and benefits of treatment need to be discussed with patients, he added.
Over a series of tweets, Rebecca J. Lee, PhD, NIHR clinical lecturer in medical oncology at the University of Manchester, United Kingdom, said, “we need to know more” about the distant metastasis-free survival results, and that results for overall survival are “really” needed.
She also emphasized the need for biomarkers to identify those patients who are likely to benefit, and whether benefit can be upfront or early on in treatment. Dr. Lee added that, as endocrine thyroid toxicity occurs after a median of 3.3 months, “pretreatment biomarkers will be more important than on-treatment biomarkers in this setting.”
Details of the results in earlier stage disease
The KEYNOTE-716 trial enrolled patients with newly diagnosed, resected, high-risk stage 2 melanoma aged ≥ 12 years and a good performance status. The majority (~64%) had stage 2B melanoma, and the rest had stage 2C. T3b disease was present in 41% of patients, 23% had T4a disease, and 35% had T4b disease.
Patients were randomized to receive pembrolizumab or placebo.
In a subsequent part of the study, patients with recurrence will be unblended, with either crossover from the placebo to active treatment group or rechallenge with pembrolizumab for up to 2 years.
Presenting the first part, Dr. Luke said that, of 487 patients assigned to pembrolizumab, 483 started treatment, of whom 206 have completed treatment, 133 are still on therapy, and 144 have discontinued.
In the placebo group, 489 patients were assigned and 486 began treatment. Of those, 229 completed treatment, 152 are still ongoing, and 105 discontinued.
The two groups were well balanced in terms of baseline characteristics. The median age was approximately 60 years, with only one patient enrolled who was aged 12-17 years.
At 12 months, the study met its primary endpoint.
Relapse-fee survival was 90.5% in patients treated with pembrolizumab versus 83.1% in the placebo group, at a hazard ratio for recurrence of 0.65 (P = .00658).
“Despite this trial hitting this primary endpoint very early, there are a number of patients who are censored later in the curves,” Dr. Luke said, adding that “we will continue to see these data mature.”
“In fact, it’s our full expectation that curves will continue to separate over time.”
When looking at key subgroups, Dr. Luke showed that the results favored pembrolizumab when stratifying patients by age, gender, race, and performance status.
Interestingly, patients with T3b disease did a lot better on pembrolizumab compared with those who had T4b disease, at a hazard ratio for recurrence of 0.44 versus 0.94.
Data on recurrence patterns revealed that 11.1% of patients taking pembrolizumab had an event, with 6.4% experiencing skin and/or lymph node regional recurrence and 4.7% distant recurrence.
In the placebo group, 16.8% of patients had a recurrence event, with 8.4% having a loco-regional recurrence and 7.8% a distant recurrence.
Dr. Luke explained that this equates to an approximate 40% reduction in distant recurrence with pembrolizumab over placebo.
Finally, the researchers examined change in global health status on the EORTC QLQ-C30 quality of life score. Examining mean change over time, they found that there were no clinically meaningful changes, and the scores in the pembrolizumab and placebo groups tracked each other during the course of follow-up.
Quality of life was, therefore, “only minimally changed,” Dr. Luke said.
The study was funded by MSD. Dr. Luke and Dr. Hamid have declared relationships with multiple companies.
A version of this article first appeared on Medscape.com.
However, the results raise many questions, says an expert invited to discuss the new data.
Adjuvant pembrolizumab is already approved in the United States for use in patients with melanoma with lymph node involvement following complete resection, having been shown to prolong both recurrence-free and distant metastasis-free survival (DMFS) in stage 3 melanoma.
This latest trial involved patients with slightly earlier disease, those with resected stage 2B and 2C melanoma. These patients are at “high risk” of disease recurrence and have similar outcomes to stage 3A and 3B melanoma patients, explained study presenter Jason J. Luke, MD, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, Pittsburgh.
Results from the KEYNOTE-716 trial showed that adjuvant pembrolizumab is also beneficial in this earlier stage disease: it improved recurrence-free survival (RFS) by 35% and improved distant metastasis-free survival by 40% compared with placebo.
Adjuvant pembrolizumab is an “effective treatment option with a favorable benefit-risk profile for patients with high-risk stage 2 melanoma,” Dr. Luke concluded.
The manufacturer, Merck, has said that these new results have already been accepted for priority review by the U.S. Food and Drug Administration, making it likely that the indication will be extended to include patients with earlier disease.
Dr. Luke presented the results at the European Society of Medical Oncology 2021 annual meeting.
Invited discussant Omid Hamid, MD, chief of research/immuno-oncology, the Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, said that Dr. Luke’s presentation was “amazing.”
However, these new results have “sabotaged how we think about how we treat our patients and how we’re going to think about what we do in the future.”
Dr. Hamid noted that the incidence of stage 2B and 2C melanoma is “equal” to that of stage 3 disease, “so with a proposed approval” of pembrolizumab in this earlier setting, “we will have a lot more patients” to treat earlier in their disease course.
Of course, this raises the inevitable question of how to treat these patients when they relapse, and how to treat these patients in the metastatic setting “having already exhausted single-agent PD-1 therapy,” he commented.
Dr. Hamid said that the current results also reveal the “current problem” with adjuvant therapy, which is that “we don’t know who benefits,” and there is a subset patients who “never recur” even if they are untreated.
So the questions are: “How come all get treated? What about the risks of toxicity? The costs? And where do we fit these patients into clinic?”
As with so many presentations of immunotherapy trial data, the need for biomarkers was raised, with Dr. Hamid emphasizing the need for predictive biomarkers that could exclude patients, and save them from toxicity.
He noted that there were data with another checkpoint inhibitor, nivolumab (Opdivo), in the adjuvant setting (from the CheckMate 238 trial) that suggested higher tumor mutation burden and tumor interferon-gamma levels could play a role, and he hopes that similar data may be available from this latest trial.
Also, there are ongoing and upcoming trials in patients with stage 2B and 2C melanoma that may answer some of the outstanding questions, including a study of neoadjuvant PD-1 blockade before resection, and the DETECTION trial, which is exploring circulating tumor DNA-guided therapy postsurgery.
Then there is the NivoMela trial that will look at nivolumab in stage 2A as well as 2B and 2C disease, while the REFINE trial will assess whether giving immunotherapy less often to patients with advanced cancer, including those with melanoma, results in fewer side effects while continuing to be effective.
The current results also raise the question of whether to go “earlier and earlier” with adjuvant immunotherapy into “poor risk” stage 1 melanoma, which is already being tried in the United States, although there is “no clear understanding of what to do for those patients.”
Overall, Dr. Hamid said that the results of KEYNOTE-716 have “created more questions than answers,” including its impact on the inclusion criteria for phase 3/4 clinical trials, “which now exclude patients who have received adjuvant therapy within 6 months.”
“That will have to change,” he suggested.
Some of the questions raised by Dr. Hamid were discussed on social media, sparking a lively Twitter debate on how best to take the results forward and into the clinic.
Florentia Dimitriou, MD, a dermatology consultant in the Skin Cancer Clinic, University Hospital Zurich, Switzerland, said the data were “great” but she was “still unclear” over who needs adjuvant immunotherapy in this setting.
She also emphasized that, for her, the greater RFS benefit seen in T3b than in T4b disease “doesn’t make sense,” and she also highlighted the finding of long-term toxicity in approximately 18% of patients.
Dr. Luke replied that he agrees that the T3b/T4b results are puzzling but he said the event rate was “low” and the data are “immature,” and that he hopes to have “more info soon.”
He acknowledged that around 18% of patients taking pembrolizumab went on to receive hormone therapy for adverse events, including 13.9% due to hypothyroidism, and others including hypophysitis, adrenal sufficiency, and type 1 diabetes. However, he also pointed out that about 5% of patients in this study had background thyroid issues. The risks and benefits of treatment need to be discussed with patients, he added.
Over a series of tweets, Rebecca J. Lee, PhD, NIHR clinical lecturer in medical oncology at the University of Manchester, United Kingdom, said, “we need to know more” about the distant metastasis-free survival results, and that results for overall survival are “really” needed.
She also emphasized the need for biomarkers to identify those patients who are likely to benefit, and whether benefit can be upfront or early on in treatment. Dr. Lee added that, as endocrine thyroid toxicity occurs after a median of 3.3 months, “pretreatment biomarkers will be more important than on-treatment biomarkers in this setting.”
Details of the results in earlier stage disease
The KEYNOTE-716 trial enrolled patients with newly diagnosed, resected, high-risk stage 2 melanoma aged ≥ 12 years and a good performance status. The majority (~64%) had stage 2B melanoma, and the rest had stage 2C. T3b disease was present in 41% of patients, 23% had T4a disease, and 35% had T4b disease.
Patients were randomized to receive pembrolizumab or placebo.
In a subsequent part of the study, patients with recurrence will be unblended, with either crossover from the placebo to active treatment group or rechallenge with pembrolizumab for up to 2 years.
Presenting the first part, Dr. Luke said that, of 487 patients assigned to pembrolizumab, 483 started treatment, of whom 206 have completed treatment, 133 are still on therapy, and 144 have discontinued.
In the placebo group, 489 patients were assigned and 486 began treatment. Of those, 229 completed treatment, 152 are still ongoing, and 105 discontinued.
The two groups were well balanced in terms of baseline characteristics. The median age was approximately 60 years, with only one patient enrolled who was aged 12-17 years.
At 12 months, the study met its primary endpoint.
Relapse-fee survival was 90.5% in patients treated with pembrolizumab versus 83.1% in the placebo group, at a hazard ratio for recurrence of 0.65 (P = .00658).
“Despite this trial hitting this primary endpoint very early, there are a number of patients who are censored later in the curves,” Dr. Luke said, adding that “we will continue to see these data mature.”
“In fact, it’s our full expectation that curves will continue to separate over time.”
When looking at key subgroups, Dr. Luke showed that the results favored pembrolizumab when stratifying patients by age, gender, race, and performance status.
Interestingly, patients with T3b disease did a lot better on pembrolizumab compared with those who had T4b disease, at a hazard ratio for recurrence of 0.44 versus 0.94.
Data on recurrence patterns revealed that 11.1% of patients taking pembrolizumab had an event, with 6.4% experiencing skin and/or lymph node regional recurrence and 4.7% distant recurrence.
In the placebo group, 16.8% of patients had a recurrence event, with 8.4% having a loco-regional recurrence and 7.8% a distant recurrence.
Dr. Luke explained that this equates to an approximate 40% reduction in distant recurrence with pembrolizumab over placebo.
Finally, the researchers examined change in global health status on the EORTC QLQ-C30 quality of life score. Examining mean change over time, they found that there were no clinically meaningful changes, and the scores in the pembrolizumab and placebo groups tracked each other during the course of follow-up.
Quality of life was, therefore, “only minimally changed,” Dr. Luke said.
The study was funded by MSD. Dr. Luke and Dr. Hamid have declared relationships with multiple companies.
A version of this article first appeared on Medscape.com.
However, the results raise many questions, says an expert invited to discuss the new data.
Adjuvant pembrolizumab is already approved in the United States for use in patients with melanoma with lymph node involvement following complete resection, having been shown to prolong both recurrence-free and distant metastasis-free survival (DMFS) in stage 3 melanoma.
This latest trial involved patients with slightly earlier disease, those with resected stage 2B and 2C melanoma. These patients are at “high risk” of disease recurrence and have similar outcomes to stage 3A and 3B melanoma patients, explained study presenter Jason J. Luke, MD, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, Pittsburgh.
Results from the KEYNOTE-716 trial showed that adjuvant pembrolizumab is also beneficial in this earlier stage disease: it improved recurrence-free survival (RFS) by 35% and improved distant metastasis-free survival by 40% compared with placebo.
Adjuvant pembrolizumab is an “effective treatment option with a favorable benefit-risk profile for patients with high-risk stage 2 melanoma,” Dr. Luke concluded.
The manufacturer, Merck, has said that these new results have already been accepted for priority review by the U.S. Food and Drug Administration, making it likely that the indication will be extended to include patients with earlier disease.
Dr. Luke presented the results at the European Society of Medical Oncology 2021 annual meeting.
Invited discussant Omid Hamid, MD, chief of research/immuno-oncology, the Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, said that Dr. Luke’s presentation was “amazing.”
However, these new results have “sabotaged how we think about how we treat our patients and how we’re going to think about what we do in the future.”
Dr. Hamid noted that the incidence of stage 2B and 2C melanoma is “equal” to that of stage 3 disease, “so with a proposed approval” of pembrolizumab in this earlier setting, “we will have a lot more patients” to treat earlier in their disease course.
Of course, this raises the inevitable question of how to treat these patients when they relapse, and how to treat these patients in the metastatic setting “having already exhausted single-agent PD-1 therapy,” he commented.
Dr. Hamid said that the current results also reveal the “current problem” with adjuvant therapy, which is that “we don’t know who benefits,” and there is a subset patients who “never recur” even if they are untreated.
So the questions are: “How come all get treated? What about the risks of toxicity? The costs? And where do we fit these patients into clinic?”
As with so many presentations of immunotherapy trial data, the need for biomarkers was raised, with Dr. Hamid emphasizing the need for predictive biomarkers that could exclude patients, and save them from toxicity.
He noted that there were data with another checkpoint inhibitor, nivolumab (Opdivo), in the adjuvant setting (from the CheckMate 238 trial) that suggested higher tumor mutation burden and tumor interferon-gamma levels could play a role, and he hopes that similar data may be available from this latest trial.
Also, there are ongoing and upcoming trials in patients with stage 2B and 2C melanoma that may answer some of the outstanding questions, including a study of neoadjuvant PD-1 blockade before resection, and the DETECTION trial, which is exploring circulating tumor DNA-guided therapy postsurgery.
Then there is the NivoMela trial that will look at nivolumab in stage 2A as well as 2B and 2C disease, while the REFINE trial will assess whether giving immunotherapy less often to patients with advanced cancer, including those with melanoma, results in fewer side effects while continuing to be effective.
The current results also raise the question of whether to go “earlier and earlier” with adjuvant immunotherapy into “poor risk” stage 1 melanoma, which is already being tried in the United States, although there is “no clear understanding of what to do for those patients.”
Overall, Dr. Hamid said that the results of KEYNOTE-716 have “created more questions than answers,” including its impact on the inclusion criteria for phase 3/4 clinical trials, “which now exclude patients who have received adjuvant therapy within 6 months.”
“That will have to change,” he suggested.
Some of the questions raised by Dr. Hamid were discussed on social media, sparking a lively Twitter debate on how best to take the results forward and into the clinic.
Florentia Dimitriou, MD, a dermatology consultant in the Skin Cancer Clinic, University Hospital Zurich, Switzerland, said the data were “great” but she was “still unclear” over who needs adjuvant immunotherapy in this setting.
She also emphasized that, for her, the greater RFS benefit seen in T3b than in T4b disease “doesn’t make sense,” and she also highlighted the finding of long-term toxicity in approximately 18% of patients.
Dr. Luke replied that he agrees that the T3b/T4b results are puzzling but he said the event rate was “low” and the data are “immature,” and that he hopes to have “more info soon.”
He acknowledged that around 18% of patients taking pembrolizumab went on to receive hormone therapy for adverse events, including 13.9% due to hypothyroidism, and others including hypophysitis, adrenal sufficiency, and type 1 diabetes. However, he also pointed out that about 5% of patients in this study had background thyroid issues. The risks and benefits of treatment need to be discussed with patients, he added.
Over a series of tweets, Rebecca J. Lee, PhD, NIHR clinical lecturer in medical oncology at the University of Manchester, United Kingdom, said, “we need to know more” about the distant metastasis-free survival results, and that results for overall survival are “really” needed.
She also emphasized the need for biomarkers to identify those patients who are likely to benefit, and whether benefit can be upfront or early on in treatment. Dr. Lee added that, as endocrine thyroid toxicity occurs after a median of 3.3 months, “pretreatment biomarkers will be more important than on-treatment biomarkers in this setting.”
Details of the results in earlier stage disease
The KEYNOTE-716 trial enrolled patients with newly diagnosed, resected, high-risk stage 2 melanoma aged ≥ 12 years and a good performance status. The majority (~64%) had stage 2B melanoma, and the rest had stage 2C. T3b disease was present in 41% of patients, 23% had T4a disease, and 35% had T4b disease.
Patients were randomized to receive pembrolizumab or placebo.
In a subsequent part of the study, patients with recurrence will be unblended, with either crossover from the placebo to active treatment group or rechallenge with pembrolizumab for up to 2 years.
Presenting the first part, Dr. Luke said that, of 487 patients assigned to pembrolizumab, 483 started treatment, of whom 206 have completed treatment, 133 are still on therapy, and 144 have discontinued.
In the placebo group, 489 patients were assigned and 486 began treatment. Of those, 229 completed treatment, 152 are still ongoing, and 105 discontinued.
The two groups were well balanced in terms of baseline characteristics. The median age was approximately 60 years, with only one patient enrolled who was aged 12-17 years.
At 12 months, the study met its primary endpoint.
Relapse-fee survival was 90.5% in patients treated with pembrolizumab versus 83.1% in the placebo group, at a hazard ratio for recurrence of 0.65 (P = .00658).
“Despite this trial hitting this primary endpoint very early, there are a number of patients who are censored later in the curves,” Dr. Luke said, adding that “we will continue to see these data mature.”
“In fact, it’s our full expectation that curves will continue to separate over time.”
When looking at key subgroups, Dr. Luke showed that the results favored pembrolizumab when stratifying patients by age, gender, race, and performance status.
Interestingly, patients with T3b disease did a lot better on pembrolizumab compared with those who had T4b disease, at a hazard ratio for recurrence of 0.44 versus 0.94.
Data on recurrence patterns revealed that 11.1% of patients taking pembrolizumab had an event, with 6.4% experiencing skin and/or lymph node regional recurrence and 4.7% distant recurrence.
In the placebo group, 16.8% of patients had a recurrence event, with 8.4% having a loco-regional recurrence and 7.8% a distant recurrence.
Dr. Luke explained that this equates to an approximate 40% reduction in distant recurrence with pembrolizumab over placebo.
Finally, the researchers examined change in global health status on the EORTC QLQ-C30 quality of life score. Examining mean change over time, they found that there were no clinically meaningful changes, and the scores in the pembrolizumab and placebo groups tracked each other during the course of follow-up.
Quality of life was, therefore, “only minimally changed,” Dr. Luke said.
The study was funded by MSD. Dr. Luke and Dr. Hamid have declared relationships with multiple companies.
A version of this article first appeared on Medscape.com.
‘Urgent’ need to understand immunotherapy de-escalation in NSCLC
However, the research to date does not provide a clear picture of which patients will achieve this “exceptional and durable response” and at which point patients can safely reduce or withdraw from treatment, according to Yasushi Goto, MD, PhD, a staff doctor in the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
Dr. Goto presented the latest evidence and explored the current unknowns surrounding immunotherapy de-escalation in NSCLC in a session this week at the virtual World Conference on Lung Cancer.
In addition to a toxicity and quality-of-life benefit for patients, immunotherapy de-escalation could have a significant impact on the costs of care, Dr. Goto stressed. The rising cost of new cancer treatments represents a “crisis” in terms of the affordability of health care, he said, and reducing these costs represents an “urgent global issue.”
Evidence on discontinuing treatment
Dr. Goto kicked off the session by emphasizing how drastically immunotherapy has enhanced outcomes for patients with NSCLC and other cancers.
This success has brought a pressing clinical question to the forefront: How long should we treat patients with immunotherapy?
The question arose over 10 years ago when ipilimumab (Yervoy) was granted FDA approval for patients with metastatic melanoma, but only for a total of four doses because of the drug’s toxicity.
“However, some patients had very lasting efficacy with the drug, even after discontinuation,” Dr. Goto said, which raised the exciting prospect that patients could achieve a functional cure with immunotherapy.
Evidence highlighting this lasting effect among patients with NSCLC soon emerged as well. A 2015 study, for instance, indicated that, despite toxicities, 50% of patients receiving nivolumab (Opdivo) continued to have a treatment effect more than 9 months after their last dose.
A 2021 analysis of patients receiving pembrolizumab (Keytruda) found that 48% of patients were disease-free after 5 years, despite having discontinued treatment after 2 years.
These investigators also found that toxicities accumulated over time – new grade greater than or equal to three toxicities occurred in 10% of patients every 6 months – which makes it particularly important to consider limiting the duration of therapy, Dr. Goto noted.
Only one randomized study to date – the CheckMate 153 trial – has explicitly explored outcomes associated with discontinuing immunotherapy in patients with NSCLC. In this study, patients still receiving nivolumab after 1 year were randomized to continue or stop therapy. Both median progression-free survival and overall survival were significantly longer in patients who continued therapy versus those who stopped at 1 year.
However, Dr. Goto noted that limitations in the study design, including the fact that many patients were censored at an early stage, made the results “nonconfirmatory” and he would like to see more data.
The role of re-treatment
Finding the optimal time to discontinue treatment is critical but even if patients stop treatment before they achieve long-lasting benefits, they can still be retreated successfully.
Two recent studies examined the potential benefits of re-treatment. In the 2021 KEYNOTE-010 analysis, 21 patients received a second course of pembrolizumab, at a response rate of 53% and a disease control rate of 81%.
In another recent study, investigators found that among 78 patients with melanoma who had discontinued either nivolumab or pembrolizumab and were re-treated after disease progression, 15% (5 of 34) receiving a single anti-PD-1 agent responded to retreatment and 25% (11 of 44) escalated to nivolumab plus ipilimumab exhibited a response.
Dr. Goto noted that there are also ongoing randomized studies examining the optimal duration of immunotherapy in advanced melanoma. One that he is involved in, the SAVE study, is enrolling patients with advanced NSCLC who have responded to anti-PD-1 agents for over a year and will compare overall survival in those who stop therapy versus those who continue. In addition, given the “growing importance” of biomarkers as a prediction tool, Dr. Goto plans to integrate circulating tumor DNA testing to help identify patients more likely to benefit from therapy discontinuation.
If successful, such approaches could “disruptively decrease prescribing costs,” by lowering doses or dose frequency, shortening the treatment duration, or by substituting therapies with fewer adverse effects, Dr. Goto said.
Discussing de-escalation in practice
During the discussion period after his talk, session co-chair Loretta Erhunmwunsee, MD, City of Hope Comprehensive Cancer Center, Duarte, California, asked Dr. Goto what his current practice is in regard to de-escalation.
He replied that, in Japan, physicians are allowed to continue immunotherapy beyond 2 years, but “many patients stop their immune checkpoint inhibitor due to toxicity,” even if it is minor.
Exploring evidence surrounding the optimal duration of therapy, session cochair Bishal Gyawali, MD, PhD, Queen’s University, Kingston, Canada, pointed to collaborative studies in colon cancer that looked at chemotherapy duration, for example looking at 3 versus 6 months of treatment.
Dr. Gyawali wondered whether the same could be achieved in lung cancer to test the non-inferiority of shorter duration of immunotherapy versus continuing treatment until disease progression.
Dr. Goto noted that the biggest difference in the current context of NSCLC is the toxicity incurred by both the adjuvant chemotherapy and the immunotherapy, making the overall benefit to the patient “very difficult to show.” Consequently, patients may not be willing to join a randomized trial in which they could experience additional toxicity for uncertain benefit.
City of Hope oncologist H. Jack West, MD, who presented at the session, said he would “love to see more trials looking at de-escalation and seeing whether we do just as well on efficacy with lower toxicity and lower costs.”
Instead, “we are seeing reports of the fourth entrant into the field that just recapitulates things we already know,” which is “terribly disappointing.”
“I really wish we could vote with our feet more and not participate in trials that are completely redundant compared to what we’ve had for years already,” Dr. West said.
No funding for this study was declared. Dr. Goto disclosed relationships with AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Guardant Health, Illumina, Kyorin, MSD, Novartis, Ono Pharmaceutical, Pfizer, Shionogi Pharma, and Taiho Pharmaceutical. Dr. West disclosed relationships with AstraZeneca, EQRx, Genentech/Roche, Merck, Mirati, and Regeneron and is a regular contributor to Medscape Oncology.
A version of this article first appeared on Medscape.com.
However, the research to date does not provide a clear picture of which patients will achieve this “exceptional and durable response” and at which point patients can safely reduce or withdraw from treatment, according to Yasushi Goto, MD, PhD, a staff doctor in the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
Dr. Goto presented the latest evidence and explored the current unknowns surrounding immunotherapy de-escalation in NSCLC in a session this week at the virtual World Conference on Lung Cancer.
In addition to a toxicity and quality-of-life benefit for patients, immunotherapy de-escalation could have a significant impact on the costs of care, Dr. Goto stressed. The rising cost of new cancer treatments represents a “crisis” in terms of the affordability of health care, he said, and reducing these costs represents an “urgent global issue.”
Evidence on discontinuing treatment
Dr. Goto kicked off the session by emphasizing how drastically immunotherapy has enhanced outcomes for patients with NSCLC and other cancers.
This success has brought a pressing clinical question to the forefront: How long should we treat patients with immunotherapy?
The question arose over 10 years ago when ipilimumab (Yervoy) was granted FDA approval for patients with metastatic melanoma, but only for a total of four doses because of the drug’s toxicity.
“However, some patients had very lasting efficacy with the drug, even after discontinuation,” Dr. Goto said, which raised the exciting prospect that patients could achieve a functional cure with immunotherapy.
Evidence highlighting this lasting effect among patients with NSCLC soon emerged as well. A 2015 study, for instance, indicated that, despite toxicities, 50% of patients receiving nivolumab (Opdivo) continued to have a treatment effect more than 9 months after their last dose.
A 2021 analysis of patients receiving pembrolizumab (Keytruda) found that 48% of patients were disease-free after 5 years, despite having discontinued treatment after 2 years.
These investigators also found that toxicities accumulated over time – new grade greater than or equal to three toxicities occurred in 10% of patients every 6 months – which makes it particularly important to consider limiting the duration of therapy, Dr. Goto noted.
Only one randomized study to date – the CheckMate 153 trial – has explicitly explored outcomes associated with discontinuing immunotherapy in patients with NSCLC. In this study, patients still receiving nivolumab after 1 year were randomized to continue or stop therapy. Both median progression-free survival and overall survival were significantly longer in patients who continued therapy versus those who stopped at 1 year.
However, Dr. Goto noted that limitations in the study design, including the fact that many patients were censored at an early stage, made the results “nonconfirmatory” and he would like to see more data.
The role of re-treatment
Finding the optimal time to discontinue treatment is critical but even if patients stop treatment before they achieve long-lasting benefits, they can still be retreated successfully.
Two recent studies examined the potential benefits of re-treatment. In the 2021 KEYNOTE-010 analysis, 21 patients received a second course of pembrolizumab, at a response rate of 53% and a disease control rate of 81%.
In another recent study, investigators found that among 78 patients with melanoma who had discontinued either nivolumab or pembrolizumab and were re-treated after disease progression, 15% (5 of 34) receiving a single anti-PD-1 agent responded to retreatment and 25% (11 of 44) escalated to nivolumab plus ipilimumab exhibited a response.
Dr. Goto noted that there are also ongoing randomized studies examining the optimal duration of immunotherapy in advanced melanoma. One that he is involved in, the SAVE study, is enrolling patients with advanced NSCLC who have responded to anti-PD-1 agents for over a year and will compare overall survival in those who stop therapy versus those who continue. In addition, given the “growing importance” of biomarkers as a prediction tool, Dr. Goto plans to integrate circulating tumor DNA testing to help identify patients more likely to benefit from therapy discontinuation.
If successful, such approaches could “disruptively decrease prescribing costs,” by lowering doses or dose frequency, shortening the treatment duration, or by substituting therapies with fewer adverse effects, Dr. Goto said.
Discussing de-escalation in practice
During the discussion period after his talk, session co-chair Loretta Erhunmwunsee, MD, City of Hope Comprehensive Cancer Center, Duarte, California, asked Dr. Goto what his current practice is in regard to de-escalation.
He replied that, in Japan, physicians are allowed to continue immunotherapy beyond 2 years, but “many patients stop their immune checkpoint inhibitor due to toxicity,” even if it is minor.
Exploring evidence surrounding the optimal duration of therapy, session cochair Bishal Gyawali, MD, PhD, Queen’s University, Kingston, Canada, pointed to collaborative studies in colon cancer that looked at chemotherapy duration, for example looking at 3 versus 6 months of treatment.
Dr. Gyawali wondered whether the same could be achieved in lung cancer to test the non-inferiority of shorter duration of immunotherapy versus continuing treatment until disease progression.
Dr. Goto noted that the biggest difference in the current context of NSCLC is the toxicity incurred by both the adjuvant chemotherapy and the immunotherapy, making the overall benefit to the patient “very difficult to show.” Consequently, patients may not be willing to join a randomized trial in which they could experience additional toxicity for uncertain benefit.
City of Hope oncologist H. Jack West, MD, who presented at the session, said he would “love to see more trials looking at de-escalation and seeing whether we do just as well on efficacy with lower toxicity and lower costs.”
Instead, “we are seeing reports of the fourth entrant into the field that just recapitulates things we already know,” which is “terribly disappointing.”
“I really wish we could vote with our feet more and not participate in trials that are completely redundant compared to what we’ve had for years already,” Dr. West said.
No funding for this study was declared. Dr. Goto disclosed relationships with AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Guardant Health, Illumina, Kyorin, MSD, Novartis, Ono Pharmaceutical, Pfizer, Shionogi Pharma, and Taiho Pharmaceutical. Dr. West disclosed relationships with AstraZeneca, EQRx, Genentech/Roche, Merck, Mirati, and Regeneron and is a regular contributor to Medscape Oncology.
A version of this article first appeared on Medscape.com.
However, the research to date does not provide a clear picture of which patients will achieve this “exceptional and durable response” and at which point patients can safely reduce or withdraw from treatment, according to Yasushi Goto, MD, PhD, a staff doctor in the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo.
Dr. Goto presented the latest evidence and explored the current unknowns surrounding immunotherapy de-escalation in NSCLC in a session this week at the virtual World Conference on Lung Cancer.
In addition to a toxicity and quality-of-life benefit for patients, immunotherapy de-escalation could have a significant impact on the costs of care, Dr. Goto stressed. The rising cost of new cancer treatments represents a “crisis” in terms of the affordability of health care, he said, and reducing these costs represents an “urgent global issue.”
Evidence on discontinuing treatment
Dr. Goto kicked off the session by emphasizing how drastically immunotherapy has enhanced outcomes for patients with NSCLC and other cancers.
This success has brought a pressing clinical question to the forefront: How long should we treat patients with immunotherapy?
The question arose over 10 years ago when ipilimumab (Yervoy) was granted FDA approval for patients with metastatic melanoma, but only for a total of four doses because of the drug’s toxicity.
“However, some patients had very lasting efficacy with the drug, even after discontinuation,” Dr. Goto said, which raised the exciting prospect that patients could achieve a functional cure with immunotherapy.
Evidence highlighting this lasting effect among patients with NSCLC soon emerged as well. A 2015 study, for instance, indicated that, despite toxicities, 50% of patients receiving nivolumab (Opdivo) continued to have a treatment effect more than 9 months after their last dose.
A 2021 analysis of patients receiving pembrolizumab (Keytruda) found that 48% of patients were disease-free after 5 years, despite having discontinued treatment after 2 years.
These investigators also found that toxicities accumulated over time – new grade greater than or equal to three toxicities occurred in 10% of patients every 6 months – which makes it particularly important to consider limiting the duration of therapy, Dr. Goto noted.
Only one randomized study to date – the CheckMate 153 trial – has explicitly explored outcomes associated with discontinuing immunotherapy in patients with NSCLC. In this study, patients still receiving nivolumab after 1 year were randomized to continue or stop therapy. Both median progression-free survival and overall survival were significantly longer in patients who continued therapy versus those who stopped at 1 year.
However, Dr. Goto noted that limitations in the study design, including the fact that many patients were censored at an early stage, made the results “nonconfirmatory” and he would like to see more data.
The role of re-treatment
Finding the optimal time to discontinue treatment is critical but even if patients stop treatment before they achieve long-lasting benefits, they can still be retreated successfully.
Two recent studies examined the potential benefits of re-treatment. In the 2021 KEYNOTE-010 analysis, 21 patients received a second course of pembrolizumab, at a response rate of 53% and a disease control rate of 81%.
In another recent study, investigators found that among 78 patients with melanoma who had discontinued either nivolumab or pembrolizumab and were re-treated after disease progression, 15% (5 of 34) receiving a single anti-PD-1 agent responded to retreatment and 25% (11 of 44) escalated to nivolumab plus ipilimumab exhibited a response.
Dr. Goto noted that there are also ongoing randomized studies examining the optimal duration of immunotherapy in advanced melanoma. One that he is involved in, the SAVE study, is enrolling patients with advanced NSCLC who have responded to anti-PD-1 agents for over a year and will compare overall survival in those who stop therapy versus those who continue. In addition, given the “growing importance” of biomarkers as a prediction tool, Dr. Goto plans to integrate circulating tumor DNA testing to help identify patients more likely to benefit from therapy discontinuation.
If successful, such approaches could “disruptively decrease prescribing costs,” by lowering doses or dose frequency, shortening the treatment duration, or by substituting therapies with fewer adverse effects, Dr. Goto said.
Discussing de-escalation in practice
During the discussion period after his talk, session co-chair Loretta Erhunmwunsee, MD, City of Hope Comprehensive Cancer Center, Duarte, California, asked Dr. Goto what his current practice is in regard to de-escalation.
He replied that, in Japan, physicians are allowed to continue immunotherapy beyond 2 years, but “many patients stop their immune checkpoint inhibitor due to toxicity,” even if it is minor.
Exploring evidence surrounding the optimal duration of therapy, session cochair Bishal Gyawali, MD, PhD, Queen’s University, Kingston, Canada, pointed to collaborative studies in colon cancer that looked at chemotherapy duration, for example looking at 3 versus 6 months of treatment.
Dr. Gyawali wondered whether the same could be achieved in lung cancer to test the non-inferiority of shorter duration of immunotherapy versus continuing treatment until disease progression.
Dr. Goto noted that the biggest difference in the current context of NSCLC is the toxicity incurred by both the adjuvant chemotherapy and the immunotherapy, making the overall benefit to the patient “very difficult to show.” Consequently, patients may not be willing to join a randomized trial in which they could experience additional toxicity for uncertain benefit.
City of Hope oncologist H. Jack West, MD, who presented at the session, said he would “love to see more trials looking at de-escalation and seeing whether we do just as well on efficacy with lower toxicity and lower costs.”
Instead, “we are seeing reports of the fourth entrant into the field that just recapitulates things we already know,” which is “terribly disappointing.”
“I really wish we could vote with our feet more and not participate in trials that are completely redundant compared to what we’ve had for years already,” Dr. West said.
No funding for this study was declared. Dr. Goto disclosed relationships with AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Guardant Health, Illumina, Kyorin, MSD, Novartis, Ono Pharmaceutical, Pfizer, Shionogi Pharma, and Taiho Pharmaceutical. Dr. West disclosed relationships with AstraZeneca, EQRx, Genentech/Roche, Merck, Mirati, and Regeneron and is a regular contributor to Medscape Oncology.
A version of this article first appeared on Medscape.com.
Tackling grief, loss in patients with advanced lung cancer
Patients with life-limiting advanced lung cancer often experience intense grief and loss.
Palliative care aims “to anticipate, prevent, and reduce suffering, promote adaptive coping, and support the best possible quality of life ... regardless of the stage of the disease or the need for other therapies,” commented Andreas Charalambous, RN, PhD, assistant professor (acting) of oncology and palliative care at the Cyprus University of Technology in Limassol, Cyprus.
He was speaking at the 2021 World Conference on Lung Cancer, where he chaired a special session entitled, “Grief and Loss in Palliative Care.”
Research shows that the use of palliative care is associated with improved quality of life and lower costs of care for patients with cancer. But a 2015 Palliative Care Survey by the National Comprehensive Cancer Network found that although the majority of leading U.S. cancer centers have inpatient palliative care services, most reported insufficient capacity to meet the demand, and that home-based palliative care services and inpatient units were much less common.
Dr. Charalambous emphasized the importance of enhancing the use and quality of palliative care services for patients with advanced lung cancer.
During the session, experts discussed an array of strategies geared towards relieving physical symptoms as well as psychological and spiritual stressors.
Physical activity: Establishing what’s possible
Grief and loss are “natural and normal” reactions to advanced cancer, commented Celia Marston, MPallCare, clinical lead for occupational therapy at Peter MacCallum Cancer Centre in Melbourne, Australia.
Patients experience feelings of loss around their independence, relationships, physical and cognitive functioning, which in turn impacts their sense of identity, daily routines, and plans for the future.
According to Ms. Marston, the rapid physical decline patients experience in the last 3 months of life is particularly “distressing,” which is why helping patients continue to perform everyday tasks is so critical.
In clinical practice, this means providing patients palliative rehabilitation focused on maintaining at least a degree of their normal physical activity, which allows them “to adjust and contend with that decline,” Ms. Marston said. It also requires understanding what is important to patients and supporting those requests.
According to Ms. Marston, optimizing patient function can help maintain or slow that rate of physical decline, or sometimes improve it. But even partial activity can be “equally if not more important” than full participation in an activity. Patients “want to be active, they want to test what they can and can’t do” and establish what is possible, she said.
Nonpharmacological approaches to symptom control
Addressing strategies to relieve physical symptoms in patients with lung cancer, Alex Molassiotis, RN, PhD, chair professor of nursing at Hong Kong Polytechnic University, explored the role nonpharmacological interventions can play.
Dr. Molassiotis highlighted the 2021 American Society of Clinical Oncology guidelines for the Management of Dyspnea in Advanced Cancer, which discuss a range of nonpharmacological strategies to manage respiratory distress, in particular. These include supplemental oxygen and noninvasive ventilation as well as breathing techniques, posture, relaxation, meditation, physical and music therapy, and acupressure or reflexology.
In a 2015 randomized controlled feasibility trial, Dr. Molassiotis explored the effectiveness of one such strategy – inspiratory muscle training – in patients with lung cancer and reported improvements in the respiratory symptom cluster of breathlessness, cough, and fatigue. A 2020 trial of breathing retraining and psychosocial support for managing dyspnea in patients with lung cancer or mesothelioma also showed the intervention improved average dyspnea, control over dyspnea, and anxiety.
However, Dr. Molassiotis cautioned, many other nonpharmacological interventions have only “limited” evidence of effectiveness, and a “stronger evidence base” is required.
Physicians should nevertheless talk to patients about their respiratory symptoms and discuss the available options, taking into account the “major impact” these symptoms have on their quality of life.
Integrating psychological strategies
More than 40% of patients with advanced nonsmall cell lung cancer experience moderate to severe death anxiety, and about one in four patients with any stage of lung cancer experience significant depression and demoralization, research shows.
During the session, Gary Rodin, MD, of the Princess Margaret Cancer Centre in Toronto, stressed the “need to intervene” and outlined approaches relevant to different stages of the disease journey.
At the onset, he said, Emotion and Symptom-Focused Engagement (EASE) can help relieve patients’ physical symptoms and traumatic stress. Those with more advanced disease can receive Meaning-Centered Psychotherapy, or Managing Cancer and Living Meaningfully (CALM), which Dr. Rodin and his colleague Sarah Hales, MD, PhD, developed. And patients at the end of life may benefit from Dignity Therapy, a short form of psychotherapy focused on helping patients find comfort and meaning in their final days.
Dr. Rodin focused on the role of CALM for those with advanced disease. CALM encompasses three to six sessions of a semi-structured intervention given over several months. The intervention focuses on four domains: 1. Symptom management and communication with healthcare providers; 2. Changes in oneself and relationships with others; 3. Spirituality, or finding a sense of meaning and purpose; and 4. Approaches to sustain hope and face mortality.
Dr. Rodin led a 2018 randomized trial comparing CALM with usual care, which showed the intervention was associated with significant reductions in depression symptoms and death anxiety in patients with advanced cancer at three and six months, as well as better patient communication and preparedness for the end of life. Patients reported that the intervention gave them “complete freedom” to communicate about themselves, their condition, and their life.
Evidence-based psychological interventions “should be offered as standard of care” to patients with lung cancer, Dr. Rodin said.
Enhancing patient-doctor communication
Having conversations early on about the goals of cancer care is particularly critical, according to Rachelle E. Bernacki, MD, director of quality initiatives, psychosocial oncology, and palliative care at the Dana-Farber Cancer Institute.
These conversations between physicians, patients, and family members give patients and loved ones time to make informed decisions, improve patients’ quality of care and satisfaction, and increase the likelihood of using hospice care, Dr. Bernacki explained.
But the reality is that these conversations don’t happen often enough. Less than one third of patients with end-stage diagnoses reported having an end-of-life discussion with their physician, and when the topic does arise, it is typically a few weeks before a patient passes away.
Moreover, these conversations “often fail to address key elements of quality discussions,” Dr. Bernacki commented.
Part of the problem is that many doctors lack the necessary training, face time constraints, or are uncertain about when or how to initiate these conversations.
Although challenging, patients want to have these discussions. Nine of 10 Americans believe doctors should talk about end-of-life issues with their patients, and 75% of older patients want to know their prognosis so they can prepare for the future, make informed medical decisions, and optimize the time they have left.
Dr. Bernacki highlighted a framework that can help clinicians have productive end-of-life conversations with patients. The Serious Illness Conversation Guide, developed by Ariadne Labs and the Dana-Farber Cancer Institute, outlines key steps, which include scheduling the conversation, delivering a prognosis, and exploring what matters to the patient. The guide also explores how to communicate effectively with patients, such as asking permission and clarifying questions as well as engaging in active listening.
Above all, Dr. Bernacki stressed that physicians should “listen more than talk” and avoid providing premature assurance when addressing the prognosis. “Many fears will arise that cannot be fixed, but talking about them makes them more bearable for the patient,” she said.
Physicians experience grief, too
Patients with advanced lung cancer are not the only ones who face loss and distress. More than half of physicians treating terminally ill patients can experience burnout, according to Sonia Oyola, MD, assistant professor of family medicine at the University of Chicago Medicine.
In her presentation, Dr. Oyola highlighted strategies physicians can use to manage their grief.
The first step is simply acknowledging feelings of loss. But every physician will have a “unique way of grieving and caring for themselves,” she said.
In general, the literature supports several approaches for managing grief: engaging in death talks and self-attunement or personal awareness training as well as providing end-of-life education in medical schools.
On the personal awareness front, Dr. Oyola highlighted a narrative medicine exercise where physicians write about the patient and reflect on what moved or touched them, what surprised them, and what inspired them.
Pursuing this kind of exercise allows physicians to reflect on their experiences in a way “we often do not have the opportunity to do” and could prevent some of the “devastating consequences in our practices, such as burnout,” Dr. Oyola said.
No funding declared. Dr. Molassiotis has reported a relationship with Helsinn. No other relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
Patients with life-limiting advanced lung cancer often experience intense grief and loss.
Palliative care aims “to anticipate, prevent, and reduce suffering, promote adaptive coping, and support the best possible quality of life ... regardless of the stage of the disease or the need for other therapies,” commented Andreas Charalambous, RN, PhD, assistant professor (acting) of oncology and palliative care at the Cyprus University of Technology in Limassol, Cyprus.
He was speaking at the 2021 World Conference on Lung Cancer, where he chaired a special session entitled, “Grief and Loss in Palliative Care.”
Research shows that the use of palliative care is associated with improved quality of life and lower costs of care for patients with cancer. But a 2015 Palliative Care Survey by the National Comprehensive Cancer Network found that although the majority of leading U.S. cancer centers have inpatient palliative care services, most reported insufficient capacity to meet the demand, and that home-based palliative care services and inpatient units were much less common.
Dr. Charalambous emphasized the importance of enhancing the use and quality of palliative care services for patients with advanced lung cancer.
During the session, experts discussed an array of strategies geared towards relieving physical symptoms as well as psychological and spiritual stressors.
Physical activity: Establishing what’s possible
Grief and loss are “natural and normal” reactions to advanced cancer, commented Celia Marston, MPallCare, clinical lead for occupational therapy at Peter MacCallum Cancer Centre in Melbourne, Australia.
Patients experience feelings of loss around their independence, relationships, physical and cognitive functioning, which in turn impacts their sense of identity, daily routines, and plans for the future.
According to Ms. Marston, the rapid physical decline patients experience in the last 3 months of life is particularly “distressing,” which is why helping patients continue to perform everyday tasks is so critical.
In clinical practice, this means providing patients palliative rehabilitation focused on maintaining at least a degree of their normal physical activity, which allows them “to adjust and contend with that decline,” Ms. Marston said. It also requires understanding what is important to patients and supporting those requests.
According to Ms. Marston, optimizing patient function can help maintain or slow that rate of physical decline, or sometimes improve it. But even partial activity can be “equally if not more important” than full participation in an activity. Patients “want to be active, they want to test what they can and can’t do” and establish what is possible, she said.
Nonpharmacological approaches to symptom control
Addressing strategies to relieve physical symptoms in patients with lung cancer, Alex Molassiotis, RN, PhD, chair professor of nursing at Hong Kong Polytechnic University, explored the role nonpharmacological interventions can play.
Dr. Molassiotis highlighted the 2021 American Society of Clinical Oncology guidelines for the Management of Dyspnea in Advanced Cancer, which discuss a range of nonpharmacological strategies to manage respiratory distress, in particular. These include supplemental oxygen and noninvasive ventilation as well as breathing techniques, posture, relaxation, meditation, physical and music therapy, and acupressure or reflexology.
In a 2015 randomized controlled feasibility trial, Dr. Molassiotis explored the effectiveness of one such strategy – inspiratory muscle training – in patients with lung cancer and reported improvements in the respiratory symptom cluster of breathlessness, cough, and fatigue. A 2020 trial of breathing retraining and psychosocial support for managing dyspnea in patients with lung cancer or mesothelioma also showed the intervention improved average dyspnea, control over dyspnea, and anxiety.
However, Dr. Molassiotis cautioned, many other nonpharmacological interventions have only “limited” evidence of effectiveness, and a “stronger evidence base” is required.
Physicians should nevertheless talk to patients about their respiratory symptoms and discuss the available options, taking into account the “major impact” these symptoms have on their quality of life.
Integrating psychological strategies
More than 40% of patients with advanced nonsmall cell lung cancer experience moderate to severe death anxiety, and about one in four patients with any stage of lung cancer experience significant depression and demoralization, research shows.
During the session, Gary Rodin, MD, of the Princess Margaret Cancer Centre in Toronto, stressed the “need to intervene” and outlined approaches relevant to different stages of the disease journey.
At the onset, he said, Emotion and Symptom-Focused Engagement (EASE) can help relieve patients’ physical symptoms and traumatic stress. Those with more advanced disease can receive Meaning-Centered Psychotherapy, or Managing Cancer and Living Meaningfully (CALM), which Dr. Rodin and his colleague Sarah Hales, MD, PhD, developed. And patients at the end of life may benefit from Dignity Therapy, a short form of psychotherapy focused on helping patients find comfort and meaning in their final days.
Dr. Rodin focused on the role of CALM for those with advanced disease. CALM encompasses three to six sessions of a semi-structured intervention given over several months. The intervention focuses on four domains: 1. Symptom management and communication with healthcare providers; 2. Changes in oneself and relationships with others; 3. Spirituality, or finding a sense of meaning and purpose; and 4. Approaches to sustain hope and face mortality.
Dr. Rodin led a 2018 randomized trial comparing CALM with usual care, which showed the intervention was associated with significant reductions in depression symptoms and death anxiety in patients with advanced cancer at three and six months, as well as better patient communication and preparedness for the end of life. Patients reported that the intervention gave them “complete freedom” to communicate about themselves, their condition, and their life.
Evidence-based psychological interventions “should be offered as standard of care” to patients with lung cancer, Dr. Rodin said.
Enhancing patient-doctor communication
Having conversations early on about the goals of cancer care is particularly critical, according to Rachelle E. Bernacki, MD, director of quality initiatives, psychosocial oncology, and palliative care at the Dana-Farber Cancer Institute.
These conversations between physicians, patients, and family members give patients and loved ones time to make informed decisions, improve patients’ quality of care and satisfaction, and increase the likelihood of using hospice care, Dr. Bernacki explained.
But the reality is that these conversations don’t happen often enough. Less than one third of patients with end-stage diagnoses reported having an end-of-life discussion with their physician, and when the topic does arise, it is typically a few weeks before a patient passes away.
Moreover, these conversations “often fail to address key elements of quality discussions,” Dr. Bernacki commented.
Part of the problem is that many doctors lack the necessary training, face time constraints, or are uncertain about when or how to initiate these conversations.
Although challenging, patients want to have these discussions. Nine of 10 Americans believe doctors should talk about end-of-life issues with their patients, and 75% of older patients want to know their prognosis so they can prepare for the future, make informed medical decisions, and optimize the time they have left.
Dr. Bernacki highlighted a framework that can help clinicians have productive end-of-life conversations with patients. The Serious Illness Conversation Guide, developed by Ariadne Labs and the Dana-Farber Cancer Institute, outlines key steps, which include scheduling the conversation, delivering a prognosis, and exploring what matters to the patient. The guide also explores how to communicate effectively with patients, such as asking permission and clarifying questions as well as engaging in active listening.
Above all, Dr. Bernacki stressed that physicians should “listen more than talk” and avoid providing premature assurance when addressing the prognosis. “Many fears will arise that cannot be fixed, but talking about them makes them more bearable for the patient,” she said.
Physicians experience grief, too
Patients with advanced lung cancer are not the only ones who face loss and distress. More than half of physicians treating terminally ill patients can experience burnout, according to Sonia Oyola, MD, assistant professor of family medicine at the University of Chicago Medicine.
In her presentation, Dr. Oyola highlighted strategies physicians can use to manage their grief.
The first step is simply acknowledging feelings of loss. But every physician will have a “unique way of grieving and caring for themselves,” she said.
In general, the literature supports several approaches for managing grief: engaging in death talks and self-attunement or personal awareness training as well as providing end-of-life education in medical schools.
On the personal awareness front, Dr. Oyola highlighted a narrative medicine exercise where physicians write about the patient and reflect on what moved or touched them, what surprised them, and what inspired them.
Pursuing this kind of exercise allows physicians to reflect on their experiences in a way “we often do not have the opportunity to do” and could prevent some of the “devastating consequences in our practices, such as burnout,” Dr. Oyola said.
No funding declared. Dr. Molassiotis has reported a relationship with Helsinn. No other relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
Patients with life-limiting advanced lung cancer often experience intense grief and loss.
Palliative care aims “to anticipate, prevent, and reduce suffering, promote adaptive coping, and support the best possible quality of life ... regardless of the stage of the disease or the need for other therapies,” commented Andreas Charalambous, RN, PhD, assistant professor (acting) of oncology and palliative care at the Cyprus University of Technology in Limassol, Cyprus.
He was speaking at the 2021 World Conference on Lung Cancer, where he chaired a special session entitled, “Grief and Loss in Palliative Care.”
Research shows that the use of palliative care is associated with improved quality of life and lower costs of care for patients with cancer. But a 2015 Palliative Care Survey by the National Comprehensive Cancer Network found that although the majority of leading U.S. cancer centers have inpatient palliative care services, most reported insufficient capacity to meet the demand, and that home-based palliative care services and inpatient units were much less common.
Dr. Charalambous emphasized the importance of enhancing the use and quality of palliative care services for patients with advanced lung cancer.
During the session, experts discussed an array of strategies geared towards relieving physical symptoms as well as psychological and spiritual stressors.
Physical activity: Establishing what’s possible
Grief and loss are “natural and normal” reactions to advanced cancer, commented Celia Marston, MPallCare, clinical lead for occupational therapy at Peter MacCallum Cancer Centre in Melbourne, Australia.
Patients experience feelings of loss around their independence, relationships, physical and cognitive functioning, which in turn impacts their sense of identity, daily routines, and plans for the future.
According to Ms. Marston, the rapid physical decline patients experience in the last 3 months of life is particularly “distressing,” which is why helping patients continue to perform everyday tasks is so critical.
In clinical practice, this means providing patients palliative rehabilitation focused on maintaining at least a degree of their normal physical activity, which allows them “to adjust and contend with that decline,” Ms. Marston said. It also requires understanding what is important to patients and supporting those requests.
According to Ms. Marston, optimizing patient function can help maintain or slow that rate of physical decline, or sometimes improve it. But even partial activity can be “equally if not more important” than full participation in an activity. Patients “want to be active, they want to test what they can and can’t do” and establish what is possible, she said.
Nonpharmacological approaches to symptom control
Addressing strategies to relieve physical symptoms in patients with lung cancer, Alex Molassiotis, RN, PhD, chair professor of nursing at Hong Kong Polytechnic University, explored the role nonpharmacological interventions can play.
Dr. Molassiotis highlighted the 2021 American Society of Clinical Oncology guidelines for the Management of Dyspnea in Advanced Cancer, which discuss a range of nonpharmacological strategies to manage respiratory distress, in particular. These include supplemental oxygen and noninvasive ventilation as well as breathing techniques, posture, relaxation, meditation, physical and music therapy, and acupressure or reflexology.
In a 2015 randomized controlled feasibility trial, Dr. Molassiotis explored the effectiveness of one such strategy – inspiratory muscle training – in patients with lung cancer and reported improvements in the respiratory symptom cluster of breathlessness, cough, and fatigue. A 2020 trial of breathing retraining and psychosocial support for managing dyspnea in patients with lung cancer or mesothelioma also showed the intervention improved average dyspnea, control over dyspnea, and anxiety.
However, Dr. Molassiotis cautioned, many other nonpharmacological interventions have only “limited” evidence of effectiveness, and a “stronger evidence base” is required.
Physicians should nevertheless talk to patients about their respiratory symptoms and discuss the available options, taking into account the “major impact” these symptoms have on their quality of life.
Integrating psychological strategies
More than 40% of patients with advanced nonsmall cell lung cancer experience moderate to severe death anxiety, and about one in four patients with any stage of lung cancer experience significant depression and demoralization, research shows.
During the session, Gary Rodin, MD, of the Princess Margaret Cancer Centre in Toronto, stressed the “need to intervene” and outlined approaches relevant to different stages of the disease journey.
At the onset, he said, Emotion and Symptom-Focused Engagement (EASE) can help relieve patients’ physical symptoms and traumatic stress. Those with more advanced disease can receive Meaning-Centered Psychotherapy, or Managing Cancer and Living Meaningfully (CALM), which Dr. Rodin and his colleague Sarah Hales, MD, PhD, developed. And patients at the end of life may benefit from Dignity Therapy, a short form of psychotherapy focused on helping patients find comfort and meaning in their final days.
Dr. Rodin focused on the role of CALM for those with advanced disease. CALM encompasses three to six sessions of a semi-structured intervention given over several months. The intervention focuses on four domains: 1. Symptom management and communication with healthcare providers; 2. Changes in oneself and relationships with others; 3. Spirituality, or finding a sense of meaning and purpose; and 4. Approaches to sustain hope and face mortality.
Dr. Rodin led a 2018 randomized trial comparing CALM with usual care, which showed the intervention was associated with significant reductions in depression symptoms and death anxiety in patients with advanced cancer at three and six months, as well as better patient communication and preparedness for the end of life. Patients reported that the intervention gave them “complete freedom” to communicate about themselves, their condition, and their life.
Evidence-based psychological interventions “should be offered as standard of care” to patients with lung cancer, Dr. Rodin said.
Enhancing patient-doctor communication
Having conversations early on about the goals of cancer care is particularly critical, according to Rachelle E. Bernacki, MD, director of quality initiatives, psychosocial oncology, and palliative care at the Dana-Farber Cancer Institute.
These conversations between physicians, patients, and family members give patients and loved ones time to make informed decisions, improve patients’ quality of care and satisfaction, and increase the likelihood of using hospice care, Dr. Bernacki explained.
But the reality is that these conversations don’t happen often enough. Less than one third of patients with end-stage diagnoses reported having an end-of-life discussion with their physician, and when the topic does arise, it is typically a few weeks before a patient passes away.
Moreover, these conversations “often fail to address key elements of quality discussions,” Dr. Bernacki commented.
Part of the problem is that many doctors lack the necessary training, face time constraints, or are uncertain about when or how to initiate these conversations.
Although challenging, patients want to have these discussions. Nine of 10 Americans believe doctors should talk about end-of-life issues with their patients, and 75% of older patients want to know their prognosis so they can prepare for the future, make informed medical decisions, and optimize the time they have left.
Dr. Bernacki highlighted a framework that can help clinicians have productive end-of-life conversations with patients. The Serious Illness Conversation Guide, developed by Ariadne Labs and the Dana-Farber Cancer Institute, outlines key steps, which include scheduling the conversation, delivering a prognosis, and exploring what matters to the patient. The guide also explores how to communicate effectively with patients, such as asking permission and clarifying questions as well as engaging in active listening.
Above all, Dr. Bernacki stressed that physicians should “listen more than talk” and avoid providing premature assurance when addressing the prognosis. “Many fears will arise that cannot be fixed, but talking about them makes them more bearable for the patient,” she said.
Physicians experience grief, too
Patients with advanced lung cancer are not the only ones who face loss and distress. More than half of physicians treating terminally ill patients can experience burnout, according to Sonia Oyola, MD, assistant professor of family medicine at the University of Chicago Medicine.
In her presentation, Dr. Oyola highlighted strategies physicians can use to manage their grief.
The first step is simply acknowledging feelings of loss. But every physician will have a “unique way of grieving and caring for themselves,” she said.
In general, the literature supports several approaches for managing grief: engaging in death talks and self-attunement or personal awareness training as well as providing end-of-life education in medical schools.
On the personal awareness front, Dr. Oyola highlighted a narrative medicine exercise where physicians write about the patient and reflect on what moved or touched them, what surprised them, and what inspired them.
Pursuing this kind of exercise allows physicians to reflect on their experiences in a way “we often do not have the opportunity to do” and could prevent some of the “devastating consequences in our practices, such as burnout,” Dr. Oyola said.
No funding declared. Dr. Molassiotis has reported a relationship with Helsinn. No other relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
ESMO 2021: Impressive clinical research despite pandemic
The meeting, which will be held online from September 16 to 21, will also see headlining results from immunotherapy trials in melanoma, lung cancer, and prostate cancer, as well as studies of the impact of COVID-19 vaccination in cancer patients.
“This is the second year of the virtual ESMO meeting, and this is important because the pandemic and the lockdown have impacted our clinical practice and research,” said conference press spokesman Antonio Passaro, MD, PhD, from the Division of Thoracic Oncology at the European Institute of Oncology, in Milan.
“But when you look at the submitted abstracts and the data that will be presented during ESMO, we can see that clinical research has been ‘resurrected,’“ he told this news organization.
A huge amount of “high-quality” data will be presented, said Dr. Passaro, which is “important,” inasmuch as this is the second year of the pandemic.
He underlined that it is “crucial” to remember that “the pandemic affected not only the lives and quality of life of our patients but also health care systems and the work and quality of life of health care professionals.”
A large amount of the new clinical data to be presented at the meeting will focus on the role of immune checkpoint inhibitors in various types of cancer, Dr. Passaro commented. Many of these will be featured in the three Presidential Symposia that will be held on Saturday, Sunday, and Monday.
These include KEYNOTE-716, a trial comparing the adjuvant use of pembrolizumab (Keytruda) to placebo after complete resection of high-risk stage II melanoma (abstract LBA3), and an analysis of the IMpower010 trial that will investigate the sites of relapse and subsequent therapy with atezolizumab (Tecentriq) in comparison with best supportive care after adjuvant chemotherapy in stage IB-IIIA non–small cell lung cancer (abstract LBA9).
Dr. Passaro commented that it is “interesting to note” that the immunotherapy data at ESMO 2021 will not only be in these “classical diseases in which immunotherapy improves survival” but also in different types of cancer, thus “widening the opportunity for our patients” to benefit.
There will be “important results” for immune checkpoint inhibitors for gynecologic cancers, as well as colorectal and gastric cancers, “which is a key topic for this ESMO meeting,” he said.
Other highlights from the Presidential Symposia include the following:
- Results from the phase 3 KEYNOTE-826 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer (abstract LBA2_PR)
- Results from the CheckMate 649 study, which examined nivolumab (Opdivo) plus chemotherapy or ipilimumab (Yervoy) in comparison with chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (abstract LBA7)
- Results from KRYSTAL-1, a phase 1/2 trial of the investigational agent adagrasib (MRTX849, Mirati Therapeutics) as monotherapy or combined with cetuximab for patients with colorectal cancer harboring a KRASG12C mutation (abstract LBA6)
- Data from FIRSTMAPPP, the first international randomized study of malignant progressive pheochromocytoma and paragangliomas comparing sunitinib (Sutent) with placebo (abstract 567O_PR)
- A combined analysis from the STAMPEDE protocol comparing androgen-deprivation therapy (ADT) alone to abiraterone acetate plus prednisolone, with or without enzalutamide, added to ADT for men with high-risk nonmetastatic prostate cancer (abstract LBA4_PR)
- Results from later-stage disease in men with de novo metastatic castration-sensitive prostate cancer enrolled in PEACE-1, a phase 3 trial investigating overall survival with abiraterone acetate plus prednisone (abstract LBA5_PR)
In addition, Dr. Passaro noted that data will be presented on the impact of the COVID-19 pandemic on cancer patients, as well as “interesting results” on the effect of COVID-19 vaccination on patients and their treatment, which is “crucial for all of us” to know. For example, the CAPTURE substudy of the TRACERx Renal trial will examine adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients (abstract 1557O).
Also in the same session, data will be presented from the VOICE study on vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumors (abstract LBA8).
At a press conference held ahead of the meeting, Pasi A. Jänne, MD, PhD, from the Dana Farber Cancer Center, Boston, who is the scientific co-chair of ESMO 2021, highlighted precision medicine as a key theme of the meeting.
He said that this is something the oncology community is “actively implementing worldwide to continue to make progress in cancer therapies and as such improve the outcomes of our patients.”
A version of this article first appeared on Medscape.com.
The meeting, which will be held online from September 16 to 21, will also see headlining results from immunotherapy trials in melanoma, lung cancer, and prostate cancer, as well as studies of the impact of COVID-19 vaccination in cancer patients.
“This is the second year of the virtual ESMO meeting, and this is important because the pandemic and the lockdown have impacted our clinical practice and research,” said conference press spokesman Antonio Passaro, MD, PhD, from the Division of Thoracic Oncology at the European Institute of Oncology, in Milan.
“But when you look at the submitted abstracts and the data that will be presented during ESMO, we can see that clinical research has been ‘resurrected,’“ he told this news organization.
A huge amount of “high-quality” data will be presented, said Dr. Passaro, which is “important,” inasmuch as this is the second year of the pandemic.
He underlined that it is “crucial” to remember that “the pandemic affected not only the lives and quality of life of our patients but also health care systems and the work and quality of life of health care professionals.”
A large amount of the new clinical data to be presented at the meeting will focus on the role of immune checkpoint inhibitors in various types of cancer, Dr. Passaro commented. Many of these will be featured in the three Presidential Symposia that will be held on Saturday, Sunday, and Monday.
These include KEYNOTE-716, a trial comparing the adjuvant use of pembrolizumab (Keytruda) to placebo after complete resection of high-risk stage II melanoma (abstract LBA3), and an analysis of the IMpower010 trial that will investigate the sites of relapse and subsequent therapy with atezolizumab (Tecentriq) in comparison with best supportive care after adjuvant chemotherapy in stage IB-IIIA non–small cell lung cancer (abstract LBA9).
Dr. Passaro commented that it is “interesting to note” that the immunotherapy data at ESMO 2021 will not only be in these “classical diseases in which immunotherapy improves survival” but also in different types of cancer, thus “widening the opportunity for our patients” to benefit.
There will be “important results” for immune checkpoint inhibitors for gynecologic cancers, as well as colorectal and gastric cancers, “which is a key topic for this ESMO meeting,” he said.
Other highlights from the Presidential Symposia include the following:
- Results from the phase 3 KEYNOTE-826 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer (abstract LBA2_PR)
- Results from the CheckMate 649 study, which examined nivolumab (Opdivo) plus chemotherapy or ipilimumab (Yervoy) in comparison with chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (abstract LBA7)
- Results from KRYSTAL-1, a phase 1/2 trial of the investigational agent adagrasib (MRTX849, Mirati Therapeutics) as monotherapy or combined with cetuximab for patients with colorectal cancer harboring a KRASG12C mutation (abstract LBA6)
- Data from FIRSTMAPPP, the first international randomized study of malignant progressive pheochromocytoma and paragangliomas comparing sunitinib (Sutent) with placebo (abstract 567O_PR)
- A combined analysis from the STAMPEDE protocol comparing androgen-deprivation therapy (ADT) alone to abiraterone acetate plus prednisolone, with or without enzalutamide, added to ADT for men with high-risk nonmetastatic prostate cancer (abstract LBA4_PR)
- Results from later-stage disease in men with de novo metastatic castration-sensitive prostate cancer enrolled in PEACE-1, a phase 3 trial investigating overall survival with abiraterone acetate plus prednisone (abstract LBA5_PR)
In addition, Dr. Passaro noted that data will be presented on the impact of the COVID-19 pandemic on cancer patients, as well as “interesting results” on the effect of COVID-19 vaccination on patients and their treatment, which is “crucial for all of us” to know. For example, the CAPTURE substudy of the TRACERx Renal trial will examine adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients (abstract 1557O).
Also in the same session, data will be presented from the VOICE study on vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumors (abstract LBA8).
At a press conference held ahead of the meeting, Pasi A. Jänne, MD, PhD, from the Dana Farber Cancer Center, Boston, who is the scientific co-chair of ESMO 2021, highlighted precision medicine as a key theme of the meeting.
He said that this is something the oncology community is “actively implementing worldwide to continue to make progress in cancer therapies and as such improve the outcomes of our patients.”
A version of this article first appeared on Medscape.com.
The meeting, which will be held online from September 16 to 21, will also see headlining results from immunotherapy trials in melanoma, lung cancer, and prostate cancer, as well as studies of the impact of COVID-19 vaccination in cancer patients.
“This is the second year of the virtual ESMO meeting, and this is important because the pandemic and the lockdown have impacted our clinical practice and research,” said conference press spokesman Antonio Passaro, MD, PhD, from the Division of Thoracic Oncology at the European Institute of Oncology, in Milan.
“But when you look at the submitted abstracts and the data that will be presented during ESMO, we can see that clinical research has been ‘resurrected,’“ he told this news organization.
A huge amount of “high-quality” data will be presented, said Dr. Passaro, which is “important,” inasmuch as this is the second year of the pandemic.
He underlined that it is “crucial” to remember that “the pandemic affected not only the lives and quality of life of our patients but also health care systems and the work and quality of life of health care professionals.”
A large amount of the new clinical data to be presented at the meeting will focus on the role of immune checkpoint inhibitors in various types of cancer, Dr. Passaro commented. Many of these will be featured in the three Presidential Symposia that will be held on Saturday, Sunday, and Monday.
These include KEYNOTE-716, a trial comparing the adjuvant use of pembrolizumab (Keytruda) to placebo after complete resection of high-risk stage II melanoma (abstract LBA3), and an analysis of the IMpower010 trial that will investigate the sites of relapse and subsequent therapy with atezolizumab (Tecentriq) in comparison with best supportive care after adjuvant chemotherapy in stage IB-IIIA non–small cell lung cancer (abstract LBA9).
Dr. Passaro commented that it is “interesting to note” that the immunotherapy data at ESMO 2021 will not only be in these “classical diseases in which immunotherapy improves survival” but also in different types of cancer, thus “widening the opportunity for our patients” to benefit.
There will be “important results” for immune checkpoint inhibitors for gynecologic cancers, as well as colorectal and gastric cancers, “which is a key topic for this ESMO meeting,” he said.
Other highlights from the Presidential Symposia include the following:
- Results from the phase 3 KEYNOTE-826 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer (abstract LBA2_PR)
- Results from the CheckMate 649 study, which examined nivolumab (Opdivo) plus chemotherapy or ipilimumab (Yervoy) in comparison with chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (abstract LBA7)
- Results from KRYSTAL-1, a phase 1/2 trial of the investigational agent adagrasib (MRTX849, Mirati Therapeutics) as monotherapy or combined with cetuximab for patients with colorectal cancer harboring a KRASG12C mutation (abstract LBA6)
- Data from FIRSTMAPPP, the first international randomized study of malignant progressive pheochromocytoma and paragangliomas comparing sunitinib (Sutent) with placebo (abstract 567O_PR)
- A combined analysis from the STAMPEDE protocol comparing androgen-deprivation therapy (ADT) alone to abiraterone acetate plus prednisolone, with or without enzalutamide, added to ADT for men with high-risk nonmetastatic prostate cancer (abstract LBA4_PR)
- Results from later-stage disease in men with de novo metastatic castration-sensitive prostate cancer enrolled in PEACE-1, a phase 3 trial investigating overall survival with abiraterone acetate plus prednisone (abstract LBA5_PR)
In addition, Dr. Passaro noted that data will be presented on the impact of the COVID-19 pandemic on cancer patients, as well as “interesting results” on the effect of COVID-19 vaccination on patients and their treatment, which is “crucial for all of us” to know. For example, the CAPTURE substudy of the TRACERx Renal trial will examine adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients (abstract 1557O).
Also in the same session, data will be presented from the VOICE study on vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumors (abstract LBA8).
At a press conference held ahead of the meeting, Pasi A. Jänne, MD, PhD, from the Dana Farber Cancer Center, Boston, who is the scientific co-chair of ESMO 2021, highlighted precision medicine as a key theme of the meeting.
He said that this is something the oncology community is “actively implementing worldwide to continue to make progress in cancer therapies and as such improve the outcomes of our patients.”
A version of this article first appeared on Medscape.com.
Researchers warn young adults are at highest risk of obesity
Individuals aged 18-24 years are at the highest risk of weight gain and developing overweight or obesity over the next 10 years, compared with all other adults, and should be a target for obesity prevention policies, say U.K. researchers.
The research, published online Sept. 2, 2021, in The Lancet Diabetes and Endocrinology, showed that factors more traditionally associated with obesity – such as socioeconomic status and ethnicity – play less of a role than age.
“Our results show clearly that age is the most important sociodemographic factor for BMI [body mass index] change,” lead author Michail Katsoulis, PhD, Institute of Health Informatics, University College London, said in a press release.
Cosenior author Claudia Langenberg, PhD, agreed, adding young people “go through big life changes. They may start work, go to university, or leave home for the first time,” and the habits formed during these years “may stick through adulthood.”
Current obesity prevention guidelines are mainly directed at individuals who already have obesity, the researchers said in their article.
“As the evidence presented in our study suggests, the opportunity to modify weight gain is greatest in individuals who are young and do not yet have obesity,” they observed.
“If we are serious about preventing obesity, then we should develop interventions that can be targeted and are relevant for young adults,” added Dr. Langenberg, of the MRC Epidemiology Unit, University of Cambridge, (England), and Berlin Institute of Health.
Risks for higher BMI substantially greater in the youngest adults
The researchers gathered data on more than 2 million adults aged 18-74 years registered with general practitioners in England. Participants had BMI and weight measurements recorded between Jan. 1, 1998, and June 30, 2016, with at least 1 year of follow-up. Overall, 58% were women, 76% were White, 9% had prevalent cardiovascular disease, and 4% had prevalent cancer.
Changes in BMI were assessed at 1 year, 5 years, and 10 years.
At 10 years, adults aged 18-24 years had the highest risk of transitioning from normal weight to overweight or obesity, compared with adults aged 65-74 years, at a greatest absolute risk of 37% versus 24% (odds ratio, 4.22).
Moreover, the results showed that adults aged 18-24 years who were already overweight or obese had a greater risk of transitioning to a higher BMI category during follow-up versus the oldest participants.
They had an absolute risk of 42% versus 18% of transitioning from overweight to class 1 and 2 obesity (OR, 4.60), and an absolute risk of transitioning from class 1 and 2 obesity to class 3 obesity of 22% versus 5% (OR, 5.87).
Online risk calculator and YouTube video help explain findings
While factors other than age were associated with transitioning to a higher BMI category, the association was less pronounced.
For example, the OR of transitioning from normal weight to overweight or obesity in the most socially deprived versus the least deprived areas was 1.23 in men and 1.12 in women. The OR for making the same transition in Black versus White individuals was 1.13.
The findings allowed the researchers to develop a series of nomograms to determine an individual’s absolute risk of transitioning to a higher BMI category over 10 years based on their baseline BMI category, age, sex, and Index of Multiple Deprivation quintile.
“We show that, within each stratum, the risks for transitioning to higher BMI categories were substantially higher in the youngest adult age group than in older age groups,” the team writes.
From this, they developed an open-access online risk calculator to help individuals calculate their risk of weight change over the next 1, 5, and 10 years. The calculator takes into account current weight, height, age, sex, ethnicity, and socioeconomic-area characteristics.
They have also posted a video on YouTube to help explain their findings.
COVID and obesity pandemics collide
Cosenior author Harry Hemingway, MD, PhD, also of University College London, believes that focusing on this young age group is especially critical now because of the COVID-19 pandemic.
“Calculating personal risk of transitioning to a higher weight category is important” as COVID-19 “collides with the obesity pandemic,” he said, noting that “people are exercising less and finding it harder to eat healthy diets during lockdowns.
“Health systems like the NHS [National Health Service] need to identify new ways to prevent obesity and its consequences,” he continued. “This study demonstrates that NHS data collected over time in primary care holds an important key to unlocking new insights for public health action.”
The study was funded by the British Heart Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Individuals aged 18-24 years are at the highest risk of weight gain and developing overweight or obesity over the next 10 years, compared with all other adults, and should be a target for obesity prevention policies, say U.K. researchers.
The research, published online Sept. 2, 2021, in The Lancet Diabetes and Endocrinology, showed that factors more traditionally associated with obesity – such as socioeconomic status and ethnicity – play less of a role than age.
“Our results show clearly that age is the most important sociodemographic factor for BMI [body mass index] change,” lead author Michail Katsoulis, PhD, Institute of Health Informatics, University College London, said in a press release.
Cosenior author Claudia Langenberg, PhD, agreed, adding young people “go through big life changes. They may start work, go to university, or leave home for the first time,” and the habits formed during these years “may stick through adulthood.”
Current obesity prevention guidelines are mainly directed at individuals who already have obesity, the researchers said in their article.
“As the evidence presented in our study suggests, the opportunity to modify weight gain is greatest in individuals who are young and do not yet have obesity,” they observed.
“If we are serious about preventing obesity, then we should develop interventions that can be targeted and are relevant for young adults,” added Dr. Langenberg, of the MRC Epidemiology Unit, University of Cambridge, (England), and Berlin Institute of Health.
Risks for higher BMI substantially greater in the youngest adults
The researchers gathered data on more than 2 million adults aged 18-74 years registered with general practitioners in England. Participants had BMI and weight measurements recorded between Jan. 1, 1998, and June 30, 2016, with at least 1 year of follow-up. Overall, 58% were women, 76% were White, 9% had prevalent cardiovascular disease, and 4% had prevalent cancer.
Changes in BMI were assessed at 1 year, 5 years, and 10 years.
At 10 years, adults aged 18-24 years had the highest risk of transitioning from normal weight to overweight or obesity, compared with adults aged 65-74 years, at a greatest absolute risk of 37% versus 24% (odds ratio, 4.22).
Moreover, the results showed that adults aged 18-24 years who were already overweight or obese had a greater risk of transitioning to a higher BMI category during follow-up versus the oldest participants.
They had an absolute risk of 42% versus 18% of transitioning from overweight to class 1 and 2 obesity (OR, 4.60), and an absolute risk of transitioning from class 1 and 2 obesity to class 3 obesity of 22% versus 5% (OR, 5.87).
Online risk calculator and YouTube video help explain findings
While factors other than age were associated with transitioning to a higher BMI category, the association was less pronounced.
For example, the OR of transitioning from normal weight to overweight or obesity in the most socially deprived versus the least deprived areas was 1.23 in men and 1.12 in women. The OR for making the same transition in Black versus White individuals was 1.13.
The findings allowed the researchers to develop a series of nomograms to determine an individual’s absolute risk of transitioning to a higher BMI category over 10 years based on their baseline BMI category, age, sex, and Index of Multiple Deprivation quintile.
“We show that, within each stratum, the risks for transitioning to higher BMI categories were substantially higher in the youngest adult age group than in older age groups,” the team writes.
From this, they developed an open-access online risk calculator to help individuals calculate their risk of weight change over the next 1, 5, and 10 years. The calculator takes into account current weight, height, age, sex, ethnicity, and socioeconomic-area characteristics.
They have also posted a video on YouTube to help explain their findings.
COVID and obesity pandemics collide
Cosenior author Harry Hemingway, MD, PhD, also of University College London, believes that focusing on this young age group is especially critical now because of the COVID-19 pandemic.
“Calculating personal risk of transitioning to a higher weight category is important” as COVID-19 “collides with the obesity pandemic,” he said, noting that “people are exercising less and finding it harder to eat healthy diets during lockdowns.
“Health systems like the NHS [National Health Service] need to identify new ways to prevent obesity and its consequences,” he continued. “This study demonstrates that NHS data collected over time in primary care holds an important key to unlocking new insights for public health action.”
The study was funded by the British Heart Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Individuals aged 18-24 years are at the highest risk of weight gain and developing overweight or obesity over the next 10 years, compared with all other adults, and should be a target for obesity prevention policies, say U.K. researchers.
The research, published online Sept. 2, 2021, in The Lancet Diabetes and Endocrinology, showed that factors more traditionally associated with obesity – such as socioeconomic status and ethnicity – play less of a role than age.
“Our results show clearly that age is the most important sociodemographic factor for BMI [body mass index] change,” lead author Michail Katsoulis, PhD, Institute of Health Informatics, University College London, said in a press release.
Cosenior author Claudia Langenberg, PhD, agreed, adding young people “go through big life changes. They may start work, go to university, or leave home for the first time,” and the habits formed during these years “may stick through adulthood.”
Current obesity prevention guidelines are mainly directed at individuals who already have obesity, the researchers said in their article.
“As the evidence presented in our study suggests, the opportunity to modify weight gain is greatest in individuals who are young and do not yet have obesity,” they observed.
“If we are serious about preventing obesity, then we should develop interventions that can be targeted and are relevant for young adults,” added Dr. Langenberg, of the MRC Epidemiology Unit, University of Cambridge, (England), and Berlin Institute of Health.
Risks for higher BMI substantially greater in the youngest adults
The researchers gathered data on more than 2 million adults aged 18-74 years registered with general practitioners in England. Participants had BMI and weight measurements recorded between Jan. 1, 1998, and June 30, 2016, with at least 1 year of follow-up. Overall, 58% were women, 76% were White, 9% had prevalent cardiovascular disease, and 4% had prevalent cancer.
Changes in BMI were assessed at 1 year, 5 years, and 10 years.
At 10 years, adults aged 18-24 years had the highest risk of transitioning from normal weight to overweight or obesity, compared with adults aged 65-74 years, at a greatest absolute risk of 37% versus 24% (odds ratio, 4.22).
Moreover, the results showed that adults aged 18-24 years who were already overweight or obese had a greater risk of transitioning to a higher BMI category during follow-up versus the oldest participants.
They had an absolute risk of 42% versus 18% of transitioning from overweight to class 1 and 2 obesity (OR, 4.60), and an absolute risk of transitioning from class 1 and 2 obesity to class 3 obesity of 22% versus 5% (OR, 5.87).
Online risk calculator and YouTube video help explain findings
While factors other than age were associated with transitioning to a higher BMI category, the association was less pronounced.
For example, the OR of transitioning from normal weight to overweight or obesity in the most socially deprived versus the least deprived areas was 1.23 in men and 1.12 in women. The OR for making the same transition in Black versus White individuals was 1.13.
The findings allowed the researchers to develop a series of nomograms to determine an individual’s absolute risk of transitioning to a higher BMI category over 10 years based on their baseline BMI category, age, sex, and Index of Multiple Deprivation quintile.
“We show that, within each stratum, the risks for transitioning to higher BMI categories were substantially higher in the youngest adult age group than in older age groups,” the team writes.
From this, they developed an open-access online risk calculator to help individuals calculate their risk of weight change over the next 1, 5, and 10 years. The calculator takes into account current weight, height, age, sex, ethnicity, and socioeconomic-area characteristics.
They have also posted a video on YouTube to help explain their findings.
COVID and obesity pandemics collide
Cosenior author Harry Hemingway, MD, PhD, also of University College London, believes that focusing on this young age group is especially critical now because of the COVID-19 pandemic.
“Calculating personal risk of transitioning to a higher weight category is important” as COVID-19 “collides with the obesity pandemic,” he said, noting that “people are exercising less and finding it harder to eat healthy diets during lockdowns.
“Health systems like the NHS [National Health Service] need to identify new ways to prevent obesity and its consequences,” he continued. “This study demonstrates that NHS data collected over time in primary care holds an important key to unlocking new insights for public health action.”
The study was funded by the British Heart Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
POSEIDON: Two ICIs plus chemo up survival in mNSCLC
The study involved over 1,000 patients with stage IV NSCLC. Participants were randomly assigned to receive either two ICIs (tremelimumab and durvalumab [Imfinzi]) plus chemotherapy, or one immunotherapy (durvalumab) plus chemotherapy, or chemotherapy alone.
Adding durvalumab to chemotherapy significantly improved PFS by 26% but did not significantly improve OS, the researchers reported. However, adding both tremelimumab and durvalumab significantly increased both PFS (by 28%) and OS (by 23%). Median OS was 14.0 months versus 11.7 months for chemotherapy.
The results were presented on Sept. 9 at a presidential symposium of the World Conference on Lung Cancer 2021.
The two immunotherapies act at different immune checkpoints – tremelimumab acts at CTLA-4, and durvalumab acts at programmed death–1/PD–ligand 1 (PD-L1). Both drugs are from AstraZeneca, which sponsored the POSEIDON trial.
With no new safety signals identified, the triple therapy combination “represents a potential new frontline treatment option for metastatic non–small cell lung cancer,” said lead researcher Melissa L. Johnson, MD, from the Sarah Cannon Research Institute, Nashville, Tenn.
Reacting to the new results in a discussion of the paper, Julie R. Brahmer, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, said that, with so many first-line treatment choices now available for advanced NSCLC, she feels like “a kid in the candy store.”
POSEIDON may give her “another choice,” but she pointed out that there are some aspects of the study to consider.
The study required patients to undergo four cycles of chemotherapy along with immunotherapy, “which certainly is standard in many of our practices.”
However, only two cycles of chemotherapy were given in the CheckMate 9LA trial, in which nivolumab (Opdivo) and ipilimumab (Yervoy) were added to chemotherapy for the treatment of stage IV NSCLC. This combination of immunotherapies, which block CTLA-4 and PD-1, is similar to the combination that was studied in the current trial, and it is already approved for use in some patients with lung cancer.
“Also key to point out,” said Dr. Brahmer, is that, in the POSEIDON trial, “there was a trend toward more poor prognostic factors in the chemotherapy arm, where these patients had more liver or central nervous system metastases.”
Despite these differences, the survival outcomes were similar in the two trials, and in both trials, the tails of the curves indicate that “we need to see long-term data” to determine whether the benefit is ongoing.
Which patients for which combos?
Considering all the data from key trials in advanced NSCLC, Dr. Brahmer said that she believes that, for patients with high PD-L1 expression, treatment with a single immunotherapy directed against PD-1 or PD-L1 “is appropriate” and that she didn’t see that adding a CTLA-4 inhibitor to the PD-L1 inhibitor and chemotherapy would give any advantage.
“But for PD-L1–negative disease, I do think CTLA-4 antibodies seem to provide a benefit, specifically seen in the CheckMate studies,” particularly for patients with squamous disease, although she noted that in POSEIDON, histology and PD-L1 status have not been analyzed.
Dr. Brahmer concluded that, although the triple therapy improved survival outcomes in the current study, several key questions remain.
These include determining what CTLA-4 inhibition adds to PD-L1 blockade and asking whether the “slightly increased toxicity” is “worth the slightly increased long-term duration of response” and improved survival outcomes.
Furthermore, it needs to be determined “which populations truly need” the combined approach; “to get to this, we need to find the biomarker for CTLA-4 benefit,” Dr. Brahmer said.
She also noted “a practical question: Is there room in the clinic for another CTLA-4 antibody in addition to the nivolumab/ipilimumab combinations?”
This last point was appreciated on social media. Jill Feldman, a lung cancer patient and advocate, described it on Twitter as a “great question.”
She said that, for her, “options equal hope,” but that it is “critical” to give the “best treatment first. ... So as a patient, I would ask: How do I know/you know which treatment would be best for me?”
With “so many options in the first-line setting,” subsets of patients who may benefit from quadruplet therapy versus monotherapy need to be defined, commented Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia. He added that “PD-L1 may be one biomarker, but we need more.”
More details of the POSEIDON trial
In the POSEIDON trial, investigators had the choice of different chemotherapy regimens: platinum/gemcitabine for patients with squamous disease, platinum/pemetrexed for patients with nonsquamous disease, and nab-paclitaxel/carboplatin for patients with disease of either histology, Dr. Johnson reported.
It is noteworthy that the majority of patients were from Eastern Europe and Asia, “and the proportion of squamous patients enrolled was higher than is typically seen in mixed histology lung cancer studies,” she added.
The patients were stratified by PD-L1 expression at a cutoff of 50%, disease stage, and tumor histology.
Overall, 1,013 patients were enrolled. The three treatment arms were relatively well balanced in terms of baseline characteristics.
Dr. Johnson noted that there were “a few minor imbalances” in the durvalumab plus tremelimumab arm, with “fewer females, fewer Asians, and fewer never-smokers relative to the other two arms.”
The primary endpoint analysis after a median follow-up of 10.3 months demonstrated that PFS was significantly improved with durvalumab plus chemotherapy over chemotherapy alone, at a median of 5.5 months versus 4.8 months (hazard ratio, 0.74; P = .00093).
Although OS improved numerically with the addition of durvalumab to chemotherapy, it did not reach significance (13.3 months vs. 11.7 months with chemotherapy alone; HR, 0.86; P = .07581).
The positive PFS benefit with durvalumab plus chemotherapy triggered a secondary endpoint analysis, which showed that adding tremelimumab to durvalumab plus chemotherapy improved both survival outcomes.
Median PFS with the triple combination therapy was 6.2 months, significantly longer than the 4.8 months seen with chemotherapy alone (HR, 0.72; P = .00031).
At 12 months, 26.6% of patients who underwent treatment with durvalumab plus tremelimumab plus chemotherapy had not experienced disease progression, compared with 13.1% in the chemotherapy-alone arm.
OS was also significantly improved, at 14.0 months among patients in the triple therapy arm versus 11.7 in the chemotherapy-alone arm (HR, 0.77; P = .00304).
The results also showed that at 24 months, 32.9% of triple therapy patients were still alive versus 22.1% in the chemotherapy-alone arm.
Analysis indicated that “most subgroups favored the addition of immunotherapy to chemotherapy.” There was a “trend toward improved survival for all patients treated with durvalumab plus tremelimumab plus chemotherapy,” Dr. Johnson said.
This was seen “in particular for the nonsquamous patients” and for those with tumor PD-L1 expression of less than 1%, he added.
It is notable that for a large proportion of combination-therapy patients, response had continued at 12 months. This was the case for 38.9% of those who underwent treatment with durvalumab plus chemotherapy and for 49.7% of those given triple therapy versus 21.4% in the chemotherapy-alone arm.
As was seen across the whole cohort, among patients with nonsquamous disease, PFS and OS improved with the addition of immunotherapy. Of those patients with nonsquamous disease, 95.5% received pemetrexed plus platinum chemotherapy.
However, among patients with squamous tumors, of whom 88.3% received gemcitabine plus platinum chemotherapy, PFS and OS were “poor ... across all treatment arms,” Dr. Johnson reported, “with little separation of the curves.”
She highlighted the fact that the proportion of patients who experienced grade 3/4 adverse events, whether of any cause or treatment related, was only slightly higher in the two immunotherapy arms, indicating that “most events were driven by the chemotherapy.”
The rates of treatment discontinuation and adverse events leading to death were also similar across the three treatment arms, albeit they were slightly higher with the addition of immunotherapy.
Dr. Johnson also noted that, although there were more immune-mediated adverse events with durvalumab plus tremelimumab plus chemotherapy, compared with durvalumab plus chemotherapy, the “majority were grade 1/2 and were manageable.”
The most common immune-mediated events in the two immunotherapy arms were hypothyroid and hepatic events, pneumonitis, dermatitis, and rash.
The study was sponsored by AstraZeneca. Dr. Johnson reported numerous relationships with pharmaceutical companies. Dr. Brahmer reported relationships with Amgen, AstratZeneca, BMA, Genentech/Roche, Eli Lilly, Eisai, GlaxoSmithKline, Janssen, Merck, RAPT Therapeutics, Regeneron, Revolution Medicine, and Sanofi.
A version of this article first appeared on Medscape.com.
The study involved over 1,000 patients with stage IV NSCLC. Participants were randomly assigned to receive either two ICIs (tremelimumab and durvalumab [Imfinzi]) plus chemotherapy, or one immunotherapy (durvalumab) plus chemotherapy, or chemotherapy alone.
Adding durvalumab to chemotherapy significantly improved PFS by 26% but did not significantly improve OS, the researchers reported. However, adding both tremelimumab and durvalumab significantly increased both PFS (by 28%) and OS (by 23%). Median OS was 14.0 months versus 11.7 months for chemotherapy.
The results were presented on Sept. 9 at a presidential symposium of the World Conference on Lung Cancer 2021.
The two immunotherapies act at different immune checkpoints – tremelimumab acts at CTLA-4, and durvalumab acts at programmed death–1/PD–ligand 1 (PD-L1). Both drugs are from AstraZeneca, which sponsored the POSEIDON trial.
With no new safety signals identified, the triple therapy combination “represents a potential new frontline treatment option for metastatic non–small cell lung cancer,” said lead researcher Melissa L. Johnson, MD, from the Sarah Cannon Research Institute, Nashville, Tenn.
Reacting to the new results in a discussion of the paper, Julie R. Brahmer, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, said that, with so many first-line treatment choices now available for advanced NSCLC, she feels like “a kid in the candy store.”
POSEIDON may give her “another choice,” but she pointed out that there are some aspects of the study to consider.
The study required patients to undergo four cycles of chemotherapy along with immunotherapy, “which certainly is standard in many of our practices.”
However, only two cycles of chemotherapy were given in the CheckMate 9LA trial, in which nivolumab (Opdivo) and ipilimumab (Yervoy) were added to chemotherapy for the treatment of stage IV NSCLC. This combination of immunotherapies, which block CTLA-4 and PD-1, is similar to the combination that was studied in the current trial, and it is already approved for use in some patients with lung cancer.
“Also key to point out,” said Dr. Brahmer, is that, in the POSEIDON trial, “there was a trend toward more poor prognostic factors in the chemotherapy arm, where these patients had more liver or central nervous system metastases.”
Despite these differences, the survival outcomes were similar in the two trials, and in both trials, the tails of the curves indicate that “we need to see long-term data” to determine whether the benefit is ongoing.
Which patients for which combos?
Considering all the data from key trials in advanced NSCLC, Dr. Brahmer said that she believes that, for patients with high PD-L1 expression, treatment with a single immunotherapy directed against PD-1 or PD-L1 “is appropriate” and that she didn’t see that adding a CTLA-4 inhibitor to the PD-L1 inhibitor and chemotherapy would give any advantage.
“But for PD-L1–negative disease, I do think CTLA-4 antibodies seem to provide a benefit, specifically seen in the CheckMate studies,” particularly for patients with squamous disease, although she noted that in POSEIDON, histology and PD-L1 status have not been analyzed.
Dr. Brahmer concluded that, although the triple therapy improved survival outcomes in the current study, several key questions remain.
These include determining what CTLA-4 inhibition adds to PD-L1 blockade and asking whether the “slightly increased toxicity” is “worth the slightly increased long-term duration of response” and improved survival outcomes.
Furthermore, it needs to be determined “which populations truly need” the combined approach; “to get to this, we need to find the biomarker for CTLA-4 benefit,” Dr. Brahmer said.
She also noted “a practical question: Is there room in the clinic for another CTLA-4 antibody in addition to the nivolumab/ipilimumab combinations?”
This last point was appreciated on social media. Jill Feldman, a lung cancer patient and advocate, described it on Twitter as a “great question.”
She said that, for her, “options equal hope,” but that it is “critical” to give the “best treatment first. ... So as a patient, I would ask: How do I know/you know which treatment would be best for me?”
With “so many options in the first-line setting,” subsets of patients who may benefit from quadruplet therapy versus monotherapy need to be defined, commented Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia. He added that “PD-L1 may be one biomarker, but we need more.”
More details of the POSEIDON trial
In the POSEIDON trial, investigators had the choice of different chemotherapy regimens: platinum/gemcitabine for patients with squamous disease, platinum/pemetrexed for patients with nonsquamous disease, and nab-paclitaxel/carboplatin for patients with disease of either histology, Dr. Johnson reported.
It is noteworthy that the majority of patients were from Eastern Europe and Asia, “and the proportion of squamous patients enrolled was higher than is typically seen in mixed histology lung cancer studies,” she added.
The patients were stratified by PD-L1 expression at a cutoff of 50%, disease stage, and tumor histology.
Overall, 1,013 patients were enrolled. The three treatment arms were relatively well balanced in terms of baseline characteristics.
Dr. Johnson noted that there were “a few minor imbalances” in the durvalumab plus tremelimumab arm, with “fewer females, fewer Asians, and fewer never-smokers relative to the other two arms.”
The primary endpoint analysis after a median follow-up of 10.3 months demonstrated that PFS was significantly improved with durvalumab plus chemotherapy over chemotherapy alone, at a median of 5.5 months versus 4.8 months (hazard ratio, 0.74; P = .00093).
Although OS improved numerically with the addition of durvalumab to chemotherapy, it did not reach significance (13.3 months vs. 11.7 months with chemotherapy alone; HR, 0.86; P = .07581).
The positive PFS benefit with durvalumab plus chemotherapy triggered a secondary endpoint analysis, which showed that adding tremelimumab to durvalumab plus chemotherapy improved both survival outcomes.
Median PFS with the triple combination therapy was 6.2 months, significantly longer than the 4.8 months seen with chemotherapy alone (HR, 0.72; P = .00031).
At 12 months, 26.6% of patients who underwent treatment with durvalumab plus tremelimumab plus chemotherapy had not experienced disease progression, compared with 13.1% in the chemotherapy-alone arm.
OS was also significantly improved, at 14.0 months among patients in the triple therapy arm versus 11.7 in the chemotherapy-alone arm (HR, 0.77; P = .00304).
The results also showed that at 24 months, 32.9% of triple therapy patients were still alive versus 22.1% in the chemotherapy-alone arm.
Analysis indicated that “most subgroups favored the addition of immunotherapy to chemotherapy.” There was a “trend toward improved survival for all patients treated with durvalumab plus tremelimumab plus chemotherapy,” Dr. Johnson said.
This was seen “in particular for the nonsquamous patients” and for those with tumor PD-L1 expression of less than 1%, he added.
It is notable that for a large proportion of combination-therapy patients, response had continued at 12 months. This was the case for 38.9% of those who underwent treatment with durvalumab plus chemotherapy and for 49.7% of those given triple therapy versus 21.4% in the chemotherapy-alone arm.
As was seen across the whole cohort, among patients with nonsquamous disease, PFS and OS improved with the addition of immunotherapy. Of those patients with nonsquamous disease, 95.5% received pemetrexed plus platinum chemotherapy.
However, among patients with squamous tumors, of whom 88.3% received gemcitabine plus platinum chemotherapy, PFS and OS were “poor ... across all treatment arms,” Dr. Johnson reported, “with little separation of the curves.”
She highlighted the fact that the proportion of patients who experienced grade 3/4 adverse events, whether of any cause or treatment related, was only slightly higher in the two immunotherapy arms, indicating that “most events were driven by the chemotherapy.”
The rates of treatment discontinuation and adverse events leading to death were also similar across the three treatment arms, albeit they were slightly higher with the addition of immunotherapy.
Dr. Johnson also noted that, although there were more immune-mediated adverse events with durvalumab plus tremelimumab plus chemotherapy, compared with durvalumab plus chemotherapy, the “majority were grade 1/2 and were manageable.”
The most common immune-mediated events in the two immunotherapy arms were hypothyroid and hepatic events, pneumonitis, dermatitis, and rash.
The study was sponsored by AstraZeneca. Dr. Johnson reported numerous relationships with pharmaceutical companies. Dr. Brahmer reported relationships with Amgen, AstratZeneca, BMA, Genentech/Roche, Eli Lilly, Eisai, GlaxoSmithKline, Janssen, Merck, RAPT Therapeutics, Regeneron, Revolution Medicine, and Sanofi.
A version of this article first appeared on Medscape.com.
The study involved over 1,000 patients with stage IV NSCLC. Participants were randomly assigned to receive either two ICIs (tremelimumab and durvalumab [Imfinzi]) plus chemotherapy, or one immunotherapy (durvalumab) plus chemotherapy, or chemotherapy alone.
Adding durvalumab to chemotherapy significantly improved PFS by 26% but did not significantly improve OS, the researchers reported. However, adding both tremelimumab and durvalumab significantly increased both PFS (by 28%) and OS (by 23%). Median OS was 14.0 months versus 11.7 months for chemotherapy.
The results were presented on Sept. 9 at a presidential symposium of the World Conference on Lung Cancer 2021.
The two immunotherapies act at different immune checkpoints – tremelimumab acts at CTLA-4, and durvalumab acts at programmed death–1/PD–ligand 1 (PD-L1). Both drugs are from AstraZeneca, which sponsored the POSEIDON trial.
With no new safety signals identified, the triple therapy combination “represents a potential new frontline treatment option for metastatic non–small cell lung cancer,” said lead researcher Melissa L. Johnson, MD, from the Sarah Cannon Research Institute, Nashville, Tenn.
Reacting to the new results in a discussion of the paper, Julie R. Brahmer, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, said that, with so many first-line treatment choices now available for advanced NSCLC, she feels like “a kid in the candy store.”
POSEIDON may give her “another choice,” but she pointed out that there are some aspects of the study to consider.
The study required patients to undergo four cycles of chemotherapy along with immunotherapy, “which certainly is standard in many of our practices.”
However, only two cycles of chemotherapy were given in the CheckMate 9LA trial, in which nivolumab (Opdivo) and ipilimumab (Yervoy) were added to chemotherapy for the treatment of stage IV NSCLC. This combination of immunotherapies, which block CTLA-4 and PD-1, is similar to the combination that was studied in the current trial, and it is already approved for use in some patients with lung cancer.
“Also key to point out,” said Dr. Brahmer, is that, in the POSEIDON trial, “there was a trend toward more poor prognostic factors in the chemotherapy arm, where these patients had more liver or central nervous system metastases.”
Despite these differences, the survival outcomes were similar in the two trials, and in both trials, the tails of the curves indicate that “we need to see long-term data” to determine whether the benefit is ongoing.
Which patients for which combos?
Considering all the data from key trials in advanced NSCLC, Dr. Brahmer said that she believes that, for patients with high PD-L1 expression, treatment with a single immunotherapy directed against PD-1 or PD-L1 “is appropriate” and that she didn’t see that adding a CTLA-4 inhibitor to the PD-L1 inhibitor and chemotherapy would give any advantage.
“But for PD-L1–negative disease, I do think CTLA-4 antibodies seem to provide a benefit, specifically seen in the CheckMate studies,” particularly for patients with squamous disease, although she noted that in POSEIDON, histology and PD-L1 status have not been analyzed.
Dr. Brahmer concluded that, although the triple therapy improved survival outcomes in the current study, several key questions remain.
These include determining what CTLA-4 inhibition adds to PD-L1 blockade and asking whether the “slightly increased toxicity” is “worth the slightly increased long-term duration of response” and improved survival outcomes.
Furthermore, it needs to be determined “which populations truly need” the combined approach; “to get to this, we need to find the biomarker for CTLA-4 benefit,” Dr. Brahmer said.
She also noted “a practical question: Is there room in the clinic for another CTLA-4 antibody in addition to the nivolumab/ipilimumab combinations?”
This last point was appreciated on social media. Jill Feldman, a lung cancer patient and advocate, described it on Twitter as a “great question.”
She said that, for her, “options equal hope,” but that it is “critical” to give the “best treatment first. ... So as a patient, I would ask: How do I know/you know which treatment would be best for me?”
With “so many options in the first-line setting,” subsets of patients who may benefit from quadruplet therapy versus monotherapy need to be defined, commented Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia. He added that “PD-L1 may be one biomarker, but we need more.”
More details of the POSEIDON trial
In the POSEIDON trial, investigators had the choice of different chemotherapy regimens: platinum/gemcitabine for patients with squamous disease, platinum/pemetrexed for patients with nonsquamous disease, and nab-paclitaxel/carboplatin for patients with disease of either histology, Dr. Johnson reported.
It is noteworthy that the majority of patients were from Eastern Europe and Asia, “and the proportion of squamous patients enrolled was higher than is typically seen in mixed histology lung cancer studies,” she added.
The patients were stratified by PD-L1 expression at a cutoff of 50%, disease stage, and tumor histology.
Overall, 1,013 patients were enrolled. The three treatment arms were relatively well balanced in terms of baseline characteristics.
Dr. Johnson noted that there were “a few minor imbalances” in the durvalumab plus tremelimumab arm, with “fewer females, fewer Asians, and fewer never-smokers relative to the other two arms.”
The primary endpoint analysis after a median follow-up of 10.3 months demonstrated that PFS was significantly improved with durvalumab plus chemotherapy over chemotherapy alone, at a median of 5.5 months versus 4.8 months (hazard ratio, 0.74; P = .00093).
Although OS improved numerically with the addition of durvalumab to chemotherapy, it did not reach significance (13.3 months vs. 11.7 months with chemotherapy alone; HR, 0.86; P = .07581).
The positive PFS benefit with durvalumab plus chemotherapy triggered a secondary endpoint analysis, which showed that adding tremelimumab to durvalumab plus chemotherapy improved both survival outcomes.
Median PFS with the triple combination therapy was 6.2 months, significantly longer than the 4.8 months seen with chemotherapy alone (HR, 0.72; P = .00031).
At 12 months, 26.6% of patients who underwent treatment with durvalumab plus tremelimumab plus chemotherapy had not experienced disease progression, compared with 13.1% in the chemotherapy-alone arm.
OS was also significantly improved, at 14.0 months among patients in the triple therapy arm versus 11.7 in the chemotherapy-alone arm (HR, 0.77; P = .00304).
The results also showed that at 24 months, 32.9% of triple therapy patients were still alive versus 22.1% in the chemotherapy-alone arm.
Analysis indicated that “most subgroups favored the addition of immunotherapy to chemotherapy.” There was a “trend toward improved survival for all patients treated with durvalumab plus tremelimumab plus chemotherapy,” Dr. Johnson said.
This was seen “in particular for the nonsquamous patients” and for those with tumor PD-L1 expression of less than 1%, he added.
It is notable that for a large proportion of combination-therapy patients, response had continued at 12 months. This was the case for 38.9% of those who underwent treatment with durvalumab plus chemotherapy and for 49.7% of those given triple therapy versus 21.4% in the chemotherapy-alone arm.
As was seen across the whole cohort, among patients with nonsquamous disease, PFS and OS improved with the addition of immunotherapy. Of those patients with nonsquamous disease, 95.5% received pemetrexed plus platinum chemotherapy.
However, among patients with squamous tumors, of whom 88.3% received gemcitabine plus platinum chemotherapy, PFS and OS were “poor ... across all treatment arms,” Dr. Johnson reported, “with little separation of the curves.”
She highlighted the fact that the proportion of patients who experienced grade 3/4 adverse events, whether of any cause or treatment related, was only slightly higher in the two immunotherapy arms, indicating that “most events were driven by the chemotherapy.”
The rates of treatment discontinuation and adverse events leading to death were also similar across the three treatment arms, albeit they were slightly higher with the addition of immunotherapy.
Dr. Johnson also noted that, although there were more immune-mediated adverse events with durvalumab plus tremelimumab plus chemotherapy, compared with durvalumab plus chemotherapy, the “majority were grade 1/2 and were manageable.”
The most common immune-mediated events in the two immunotherapy arms were hypothyroid and hepatic events, pneumonitis, dermatitis, and rash.
The study was sponsored by AstraZeneca. Dr. Johnson reported numerous relationships with pharmaceutical companies. Dr. Brahmer reported relationships with Amgen, AstratZeneca, BMA, Genentech/Roche, Eli Lilly, Eisai, GlaxoSmithKline, Janssen, Merck, RAPT Therapeutics, Regeneron, Revolution Medicine, and Sanofi.
A version of this article first appeared on Medscape.com.
Antibiotic use and colon cancer: More evidence of link
The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.
They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.
In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.
Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).
The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.
The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.
The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.
“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.
In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.
The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.
This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”
A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.
Details of the study findings
For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.
They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.
Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.
The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.
Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).
Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).
Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.
Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).
For distal colon cancer, the relationship was “close to null.”
There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.
The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.
A version of this article first appeared on Medscape.com.
The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.
They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.
In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.
Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).
The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.
The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.
The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.
“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.
In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.
The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.
This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”
A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.
Details of the study findings
For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.
They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.
Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.
The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.
Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).
Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).
Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.
Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).
For distal colon cancer, the relationship was “close to null.”
There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.
The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.
A version of this article first appeared on Medscape.com.
The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.
They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.
In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.
Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).
The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.
The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.
The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.
“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.
In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.
The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.
This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”
A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.
Details of the study findings
For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.
They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.
Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.
The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.
Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).
Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).
Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.
Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).
For distal colon cancer, the relationship was “close to null.”
There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.
The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.
A version of this article first appeared on Medscape.com.
Pandemic strategies to boost trial enrollment should stay
Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.
These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.
These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).
Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.
Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.
Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.
These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.
“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.
The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.
Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.
This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.
Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.
Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.
The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.
“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.
However, she expressed concern that “with the telehealth visits, we can create some disparities.”
“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.
Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”
Impact on lung cancer clinical trials
The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.
Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.
The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).
The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.
The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).
Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).
Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).
“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.
Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.
This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).
Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).
The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.
Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.
The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.
A version of this article first appeared on Medscape.com.
Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.
These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.
These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).
Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.
Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.
Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.
These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.
“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.
The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.
Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.
This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.
Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.
Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.
The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.
“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.
However, she expressed concern that “with the telehealth visits, we can create some disparities.”
“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.
Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”
Impact on lung cancer clinical trials
The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.
Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.
The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).
The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.
The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).
Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).
Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).
“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.
Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.
This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).
Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).
The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.
Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.
The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.
A version of this article first appeared on Medscape.com.
Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.
These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.
These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).
Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.
Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.
Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.
These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.
“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.
The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.
Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.
This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.
Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.
Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.
The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.
“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.
However, she expressed concern that “with the telehealth visits, we can create some disparities.”
“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.
Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”
Impact on lung cancer clinical trials
The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.
Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.
The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).
The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.
The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).
Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).
Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).
“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.
Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.
This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).
Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).
The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.
Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.
The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.
A version of this article first appeared on Medscape.com.