Neil Osterweil

ORLANDO – Patients with advanced hematologic malignancies of B-cell lineage had robust immune responses following infusion of a chimeric antigen receptor (CAR)–T-cell construct designed to deliver a specific balance of antigens, investigators reported.

Adults with relapsed or refractory B-lineage acute myeloid leukemia (ALL), non–Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL) who received a CAR-T cell construct consisting of autologous CD4-positive and CD-8-positive T cells that were transduced separately, recombined, and then delivered in a single infusion had comparatively high overall response and complete response rates, reported Cameron Turtle, MBBS, PhD, from the Fred Hutchinson Cancer Research Center in Seattle.

“We know that patients have a highly variable CD4 to CD8 ratio, so by actually controlling this and separately transducing, expanding, and then reformulating in this defined composition, we’re able to eliminate one source of variability in CAR-T cell products,” Dr. Turtle said at the ASCO-SITC Clinical Immuno-Oncology Symposium.

In preclinical studies, an even balance of CD4-positive and CD8-positive central memory T cells or naive T cells evoked more potent immune responses against B-cell malignancies in mice than CD19-positive cells, he explained

To see whether this would also hold true in humans, the investigators enrolled into a phase I/II trial adults with relapsed/refractory B-cell malignancies, including ALL (36 patients), NHL (41), and CLL (24). No patients were excluded on the basis of either absolute lymphocyte, circulating tumors cells, history of stem cell transplant, or results of in vitro test expansions.

All patients underwent leukapheresis for harvesting of T-cells, and populations of CD4- and CD8-positive cells were separated and transduced with a lentiviral vector to express a CD19 CAR and a truncated human epidermal growth factor receptor that allowed tracing of the transduced cells via flow cytometry. The patients underwent lymphodepleting chemotherapy with cyclophosphamide (for the earliest patients), or cyclophosphamide plus fludarabine. Fifteen days after leukapheresis, the separated, transduced, and expanded cells were combined and delivered back to patients in a single infusion at one of three dose levels: 2 x 105, 2 x 106, or 2 x 107 CAR-T cells/kg.
 

ALL results

Two of the 36 patients with ALL died from complications of the CAR-T cell infusion process prior to evaluation. The 34 remaining patients all had morphologic bone marrow complete responses (CR). Of this group, 32 also had bone marrow CR on flow cytometry.

Using immunoglobulin H (IgH) deep sequencing in a subset of 20 patients 3 weeks after CAR-T cell infusion, the investigators could not detect the malignant IgH index clone in 13 of the patients, and found fewer than 10 copies in the bone marrow of 5 patients.

Six of seven patients with extramedullary disease at baseline had a complete response. The remaining patient in this group had an equivocal PET scan result, and experienced a relapse 2 months after assessment.

The investigators also determined that the lymphodepletion regimen may affect overall results, based on the finding that 10 of 12 patients who received cyclophosphamide alone achieved a CR, but seven of these 10 patients had a relapse within a few months. Of these seven patients. five received a second T-cell infusion, but none had significant T-cell expansion. The investigators traced the failure of the second attempt to a CD8-mediated transgene immune response to a murine single-chain variable fragment used in the construct.

For subsequent patients, they altered the lymphodepletion regimen to include fludarabine to prevent priming of the anti-CAR transgenic immune response. This modification resulted in improved progression-free survival and overall survival for subsequent patients receiving a second infusion, Dr. Turtle said.
 

NHL results

Of the 41 patients with NHL, 30 (73%) had aggressive histologies, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich large B-cell, and Burkitt lymphomas, and 11 (27%) had indolent histologies, including mantle cell and follicular lymphomas. Most of the patients had received multiple prior lines of therapy, and 19 (46%) had undergone either an autologous or allogeneic stem cell transplant.

Of the 39 evaluable patients who completed therapy, the overall response rate was 67%, including 13 (39%) with CR. Dr. Turtle noted that the CR rate was substantially higher among patients who received cyclophosphamide and fludarabine lymphodepletion, compared with cyclophosphamide alone.

There were also a few responses, including two CRs, among patients with indolent histologies, he said.

CLL, safety results

All 24 patients with CLL had previously received ibrutinib (Imbruvica). Of this group, 19 either had no significant responses to the drug, inactivating mutations, or intolerable toxicities. All but 1 of the 24 patients also had high-risk cytogenetics.

Of the 16 ibrutinib-refractory patients who were evaluable for restaging, 14 had no evidence of disease in bone marrow by flow cytometry at 4 weeks. The overall response rate in this group was 69%, which included four CRs.

Among a majority of all patients, toxicity with the CAR-T cell therapy was mild to moderate. Early cytokine changes appeared to be predictive of serious adverse events such as the cytokine release syndrome, a finding that may allow clinicians to intervene early to prevent complications, Dr. Turtle said.

In the CAR-T cell therapy, “multiple things affect the response and toxicity, including CAR T-cell dose, disease burden, the anti-CAR transgene immune response and the lymphodepletion regimen, not to mention other patient factors that we’re still sorting out,” he commented.

The trial was funded by the National Institutes of Health, Life Science Development Fund, Juno Therapeutics and the Bezos Family Foundation. Dr. Turtle disclosed consultancy, honoraria, and/or research funding from Juno Therapeutics and Seattle Genetics.

ORLANDO – Patients with advanced hematologic malignancies of B-cell lineage had robust immune responses following infusion of a chimeric antigen receptor (CAR)–T-cell construct designed to deliver a specific balance of antigens, investigators reported.

Adults with relapsed or refractory B-lineage acute myeloid leukemia (ALL), non–Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL) who received a CAR-T cell construct consisting of autologous CD4-positive and CD-8-positive T cells that were transduced separately, recombined, and then delivered in a single infusion had comparatively high overall response and complete response rates, reported Cameron Turtle, MBBS, PhD, from the Fred Hutchinson Cancer Research Center in Seattle.

“We know that patients have a highly variable CD4 to CD8 ratio, so by actually controlling this and separately transducing, expanding, and then reformulating in this defined composition, we’re able to eliminate one source of variability in CAR-T cell products,” Dr. Turtle said at the ASCO-SITC Clinical Immuno-Oncology Symposium.

In preclinical studies, an even balance of CD4-positive and CD8-positive central memory T cells or naive T cells evoked more potent immune responses against B-cell malignancies in mice than CD19-positive cells, he explained

To see whether this would also hold true in humans, the investigators enrolled into a phase I/II trial adults with relapsed/refractory B-cell malignancies, including ALL (36 patients), NHL (41), and CLL (24). No patients were excluded on the basis of either absolute lymphocyte, circulating tumors cells, history of stem cell transplant, or results of in vitro test expansions.

All patients underwent leukapheresis for harvesting of T-cells, and populations of CD4- and CD8-positive cells were separated and transduced with a lentiviral vector to express a CD19 CAR and a truncated human epidermal growth factor receptor that allowed tracing of the transduced cells via flow cytometry. The patients underwent lymphodepleting chemotherapy with cyclophosphamide (for the earliest patients), or cyclophosphamide plus fludarabine. Fifteen days after leukapheresis, the separated, transduced, and expanded cells were combined and delivered back to patients in a single infusion at one of three dose levels: 2 x 105, 2 x 106, or 2 x 107 CAR-T cells/kg.
 

ALL results

Two of the 36 patients with ALL died from complications of the CAR-T cell infusion process prior to evaluation. The 34 remaining patients all had morphologic bone marrow complete responses (CR). Of this group, 32 also had bone marrow CR on flow cytometry.

Using immunoglobulin H (IgH) deep sequencing in a subset of 20 patients 3 weeks after CAR-T cell infusion, the investigators could not detect the malignant IgH index clone in 13 of the patients, and found fewer than 10 copies in the bone marrow of 5 patients.

Six of seven patients with extramedullary disease at baseline had a complete response. The remaining patient in this group had an equivocal PET scan result, and experienced a relapse 2 months after assessment.

The investigators also determined that the lymphodepletion regimen may affect overall results, based on the finding that 10 of 12 patients who received cyclophosphamide alone achieved a CR, but seven of these 10 patients had a relapse within a few months. Of these seven patients. five received a second T-cell infusion, but none had significant T-cell expansion. The investigators traced the failure of the second attempt to a CD8-mediated transgene immune response to a murine single-chain variable fragment used in the construct.

For subsequent patients, they altered the lymphodepletion regimen to include fludarabine to prevent priming of the anti-CAR transgenic immune response. This modification resulted in improved progression-free survival and overall survival for subsequent patients receiving a second infusion, Dr. Turtle said.
 

NHL results

Of the 41 patients with NHL, 30 (73%) had aggressive histologies, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich large B-cell, and Burkitt lymphomas, and 11 (27%) had indolent histologies, including mantle cell and follicular lymphomas. Most of the patients had received multiple prior lines of therapy, and 19 (46%) had undergone either an autologous or allogeneic stem cell transplant.

Of the 39 evaluable patients who completed therapy, the overall response rate was 67%, including 13 (39%) with CR. Dr. Turtle noted that the CR rate was substantially higher among patients who received cyclophosphamide and fludarabine lymphodepletion, compared with cyclophosphamide alone.

There were also a few responses, including two CRs, among patients with indolent histologies, he said.

CLL, safety results

All 24 patients with CLL had previously received ibrutinib (Imbruvica). Of this group, 19 either had no significant responses to the drug, inactivating mutations, or intolerable toxicities. All but 1 of the 24 patients also had high-risk cytogenetics.

Of the 16 ibrutinib-refractory patients who were evaluable for restaging, 14 had no evidence of disease in bone marrow by flow cytometry at 4 weeks. The overall response rate in this group was 69%, which included four CRs.

Among a majority of all patients, toxicity with the CAR-T cell therapy was mild to moderate. Early cytokine changes appeared to be predictive of serious adverse events such as the cytokine release syndrome, a finding that may allow clinicians to intervene early to prevent complications, Dr. Turtle said.

In the CAR-T cell therapy, “multiple things affect the response and toxicity, including CAR T-cell dose, disease burden, the anti-CAR transgene immune response and the lymphodepletion regimen, not to mention other patient factors that we’re still sorting out,” he commented.

The trial was funded by the National Institutes of Health, Life Science Development Fund, Juno Therapeutics and the Bezos Family Foundation. Dr. Turtle disclosed consultancy, honoraria, and/or research funding from Juno Therapeutics and Seattle Genetics.

ORLANDO – Patients with advanced hematologic malignancies of B-cell lineage had robust immune responses following infusion of a chimeric antigen receptor (CAR)–T-cell construct designed to deliver a specific balance of antigens, investigators reported.

Adults with relapsed or refractory B-lineage acute myeloid leukemia (ALL), non–Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL) who received a CAR-T cell construct consisting of autologous CD4-positive and CD-8-positive T cells that were transduced separately, recombined, and then delivered in a single infusion had comparatively high overall response and complete response rates, reported Cameron Turtle, MBBS, PhD, from the Fred Hutchinson Cancer Research Center in Seattle.

“We know that patients have a highly variable CD4 to CD8 ratio, so by actually controlling this and separately transducing, expanding, and then reformulating in this defined composition, we’re able to eliminate one source of variability in CAR-T cell products,” Dr. Turtle said at the ASCO-SITC Clinical Immuno-Oncology Symposium.

In preclinical studies, an even balance of CD4-positive and CD8-positive central memory T cells or naive T cells evoked more potent immune responses against B-cell malignancies in mice than CD19-positive cells, he explained

To see whether this would also hold true in humans, the investigators enrolled into a phase I/II trial adults with relapsed/refractory B-cell malignancies, including ALL (36 patients), NHL (41), and CLL (24). No patients were excluded on the basis of either absolute lymphocyte, circulating tumors cells, history of stem cell transplant, or results of in vitro test expansions.

All patients underwent leukapheresis for harvesting of T-cells, and populations of CD4- and CD8-positive cells were separated and transduced with a lentiviral vector to express a CD19 CAR and a truncated human epidermal growth factor receptor that allowed tracing of the transduced cells via flow cytometry. The patients underwent lymphodepleting chemotherapy with cyclophosphamide (for the earliest patients), or cyclophosphamide plus fludarabine. Fifteen days after leukapheresis, the separated, transduced, and expanded cells were combined and delivered back to patients in a single infusion at one of three dose levels: 2 x 105, 2 x 106, or 2 x 107 CAR-T cells/kg.
 

ALL results

Two of the 36 patients with ALL died from complications of the CAR-T cell infusion process prior to evaluation. The 34 remaining patients all had morphologic bone marrow complete responses (CR). Of this group, 32 also had bone marrow CR on flow cytometry.

Using immunoglobulin H (IgH) deep sequencing in a subset of 20 patients 3 weeks after CAR-T cell infusion, the investigators could not detect the malignant IgH index clone in 13 of the patients, and found fewer than 10 copies in the bone marrow of 5 patients.

Six of seven patients with extramedullary disease at baseline had a complete response. The remaining patient in this group had an equivocal PET scan result, and experienced a relapse 2 months after assessment.

The investigators also determined that the lymphodepletion regimen may affect overall results, based on the finding that 10 of 12 patients who received cyclophosphamide alone achieved a CR, but seven of these 10 patients had a relapse within a few months. Of these seven patients. five received a second T-cell infusion, but none had significant T-cell expansion. The investigators traced the failure of the second attempt to a CD8-mediated transgene immune response to a murine single-chain variable fragment used in the construct.

For subsequent patients, they altered the lymphodepletion regimen to include fludarabine to prevent priming of the anti-CAR transgenic immune response. This modification resulted in improved progression-free survival and overall survival for subsequent patients receiving a second infusion, Dr. Turtle said.
 

NHL results

Of the 41 patients with NHL, 30 (73%) had aggressive histologies, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich large B-cell, and Burkitt lymphomas, and 11 (27%) had indolent histologies, including mantle cell and follicular lymphomas. Most of the patients had received multiple prior lines of therapy, and 19 (46%) had undergone either an autologous or allogeneic stem cell transplant.

Of the 39 evaluable patients who completed therapy, the overall response rate was 67%, including 13 (39%) with CR. Dr. Turtle noted that the CR rate was substantially higher among patients who received cyclophosphamide and fludarabine lymphodepletion, compared with cyclophosphamide alone.

There were also a few responses, including two CRs, among patients with indolent histologies, he said.

CLL, safety results

All 24 patients with CLL had previously received ibrutinib (Imbruvica). Of this group, 19 either had no significant responses to the drug, inactivating mutations, or intolerable toxicities. All but 1 of the 24 patients also had high-risk cytogenetics.

Of the 16 ibrutinib-refractory patients who were evaluable for restaging, 14 had no evidence of disease in bone marrow by flow cytometry at 4 weeks. The overall response rate in this group was 69%, which included four CRs.

Among a majority of all patients, toxicity with the CAR-T cell therapy was mild to moderate. Early cytokine changes appeared to be predictive of serious adverse events such as the cytokine release syndrome, a finding that may allow clinicians to intervene early to prevent complications, Dr. Turtle said.

In the CAR-T cell therapy, “multiple things affect the response and toxicity, including CAR T-cell dose, disease burden, the anti-CAR transgene immune response and the lymphodepletion regimen, not to mention other patient factors that we’re still sorting out,” he commented.

The trial was funded by the National Institutes of Health, Life Science Development Fund, Juno Therapeutics and the Bezos Family Foundation. Dr. Turtle disclosed consultancy, honoraria, and/or research funding from Juno Therapeutics and Seattle Genetics.

ORLANDO – In patients with advanced cervical cancer, combining chemotherapy with a vaccine against human papillomavirus (HPV) type 16 resulted in a robust, T-cell–mediated immune response and long duration survival for a large proportion of patients, reported investigators from the Netherlands.

Patients with advanced, HPV16-positive cervical cancer who were treated with standard chemotherapy and vaccinated with HPV16 synthetic long peptides (HPV16-SLP) had substantially increased T-cell responses, and these responses correlated with survival, said Marij Welters, PhD, from Leiden (the Netherlands) University Medical Center.

Neil Osterweil/Frontline Medical News

Combination required

Although therapeutic vaccination with HPV16-SLP has been shown to evoke T-cell–mediated shrinkage of HPV16-induced cervical neoplasia, the investigators found in a previous study that vaccination did not result in either tumor regression or prolonged progression-free survival of patients with advanced or recurrent HPV16-induced cervical cancer.

In the phase I trial reported here, the investigators explored whether combination HPV16-SLP with chemotherapy could potentiate T-cell responses.

In a second study, Welters et al. also showed that vaccination with HPV16-SLP after the second round of chemotherapy, when myeloid cells were at their nadir, resulted in robust T-cell responses in both mice and humans.

In the phase I trial reported here, the authors reported on the feasibility and efficacy of the technique in a larger cohort of patients with late-stage, HPV16-positive cervical cancer.

The investigators enrolled cohorts of 12 patients each and delivered one HPV16-SLP vaccine dose 2 weeks after the second, third, and fourth cycles of a total of six chemotherapy cycles with carboplatin and paclitaxel. The vaccine was test dosed at levels of 20, 40, 100, and 300 mcg/peptide, with or without 1 mcg/kg of pegylated interferon-alpha at each peptide dose level. The peptides covered the length of the HPV16 E6 and E7 proteins.

“Upon vaccination, we see a very strong T-cell response induced by the vaccine,” Dr. Welters said.

They also tested general immune responses to various microbial antigens and saw no significant differences in responses among the various dose cohorts.

Early response data was available for a total of 59 patients, 35 of whom received the vaccine/chemotherapy combination as first-line therapy and 24 of whom received it in the second line.

Two of the first-line patients had a complete response, as did one patient who received the combination as second-line therapy. Respective rates of partial responses were 22 and 5, stable disease was seen in 9 and 13 patients, and disease progression in 2 and 5 patients.

The overall response rate for patients treated in the first line was 69%, and the combined overall response and stable-disease rates were 94%. Among patients treated in the second line, the respective rates were 25% and 79%.

Median overall survival (OS) from the time of the first chemotherapy dose was 16.8 months among the first-line patients vs. 7.9 months among second-line patients (P = .0110)

At the data cutoff, median OS had not been reached for the two highest peptide dose levels (100 and 300 mcg).

The investigators also found that OS was independent of general immune status among the patients, suggesting that the benefit was derived specifically from induced T-cell responses.

‘Provocative and promising’

Invited discussant Heather McArthur, MD, MPH, from Cedars-Sinai Medical Center, Los Angeles, called the finding “provocative and promising.”

Neil Osterweil/Frontline Medical News

ORLANDO – In patients with advanced cervical cancer, combining chemotherapy with a vaccine against human papillomavirus (HPV) type 16 resulted in a robust, T-cell–mediated immune response and long duration survival for a large proportion of patients, reported investigators from the Netherlands.

Patients with advanced, HPV16-positive cervical cancer who were treated with standard chemotherapy and vaccinated with HPV16 synthetic long peptides (HPV16-SLP) had substantially increased T-cell responses, and these responses correlated with survival, said Marij Welters, PhD, from Leiden (the Netherlands) University Medical Center.

Neil Osterweil/Frontline Medical News

Combination required

Although therapeutic vaccination with HPV16-SLP has been shown to evoke T-cell–mediated shrinkage of HPV16-induced cervical neoplasia, the investigators found in a previous study that vaccination did not result in either tumor regression or prolonged progression-free survival of patients with advanced or recurrent HPV16-induced cervical cancer.

In the phase I trial reported here, the investigators explored whether combination HPV16-SLP with chemotherapy could potentiate T-cell responses.

In a second study, Welters et al. also showed that vaccination with HPV16-SLP after the second round of chemotherapy, when myeloid cells were at their nadir, resulted in robust T-cell responses in both mice and humans.

In the phase I trial reported here, the authors reported on the feasibility and efficacy of the technique in a larger cohort of patients with late-stage, HPV16-positive cervical cancer.

The investigators enrolled cohorts of 12 patients each and delivered one HPV16-SLP vaccine dose 2 weeks after the second, third, and fourth cycles of a total of six chemotherapy cycles with carboplatin and paclitaxel. The vaccine was test dosed at levels of 20, 40, 100, and 300 mcg/peptide, with or without 1 mcg/kg of pegylated interferon-alpha at each peptide dose level. The peptides covered the length of the HPV16 E6 and E7 proteins.

“Upon vaccination, we see a very strong T-cell response induced by the vaccine,” Dr. Welters said.

They also tested general immune responses to various microbial antigens and saw no significant differences in responses among the various dose cohorts.

Early response data was available for a total of 59 patients, 35 of whom received the vaccine/chemotherapy combination as first-line therapy and 24 of whom received it in the second line.

Two of the first-line patients had a complete response, as did one patient who received the combination as second-line therapy. Respective rates of partial responses were 22 and 5, stable disease was seen in 9 and 13 patients, and disease progression in 2 and 5 patients.

The overall response rate for patients treated in the first line was 69%, and the combined overall response and stable-disease rates were 94%. Among patients treated in the second line, the respective rates were 25% and 79%.

Median overall survival (OS) from the time of the first chemotherapy dose was 16.8 months among the first-line patients vs. 7.9 months among second-line patients (P = .0110)

At the data cutoff, median OS had not been reached for the two highest peptide dose levels (100 and 300 mcg).

The investigators also found that OS was independent of general immune status among the patients, suggesting that the benefit was derived specifically from induced T-cell responses.

‘Provocative and promising’

Invited discussant Heather McArthur, MD, MPH, from Cedars-Sinai Medical Center, Los Angeles, called the finding “provocative and promising.”

Neil Osterweil/Frontline Medical News

ORLANDO – In patients with advanced cervical cancer, combining chemotherapy with a vaccine against human papillomavirus (HPV) type 16 resulted in a robust, T-cell–mediated immune response and long duration survival for a large proportion of patients, reported investigators from the Netherlands.

Patients with advanced, HPV16-positive cervical cancer who were treated with standard chemotherapy and vaccinated with HPV16 synthetic long peptides (HPV16-SLP) had substantially increased T-cell responses, and these responses correlated with survival, said Marij Welters, PhD, from Leiden (the Netherlands) University Medical Center.

Neil Osterweil/Frontline Medical News

Combination required

Although therapeutic vaccination with HPV16-SLP has been shown to evoke T-cell–mediated shrinkage of HPV16-induced cervical neoplasia, the investigators found in a previous study that vaccination did not result in either tumor regression or prolonged progression-free survival of patients with advanced or recurrent HPV16-induced cervical cancer.

In the phase I trial reported here, the investigators explored whether combination HPV16-SLP with chemotherapy could potentiate T-cell responses.

In a second study, Welters et al. also showed that vaccination with HPV16-SLP after the second round of chemotherapy, when myeloid cells were at their nadir, resulted in robust T-cell responses in both mice and humans.

In the phase I trial reported here, the authors reported on the feasibility and efficacy of the technique in a larger cohort of patients with late-stage, HPV16-positive cervical cancer.

The investigators enrolled cohorts of 12 patients each and delivered one HPV16-SLP vaccine dose 2 weeks after the second, third, and fourth cycles of a total of six chemotherapy cycles with carboplatin and paclitaxel. The vaccine was test dosed at levels of 20, 40, 100, and 300 mcg/peptide, with or without 1 mcg/kg of pegylated interferon-alpha at each peptide dose level. The peptides covered the length of the HPV16 E6 and E7 proteins.

“Upon vaccination, we see a very strong T-cell response induced by the vaccine,” Dr. Welters said.

They also tested general immune responses to various microbial antigens and saw no significant differences in responses among the various dose cohorts.

Early response data was available for a total of 59 patients, 35 of whom received the vaccine/chemotherapy combination as first-line therapy and 24 of whom received it in the second line.

Two of the first-line patients had a complete response, as did one patient who received the combination as second-line therapy. Respective rates of partial responses were 22 and 5, stable disease was seen in 9 and 13 patients, and disease progression in 2 and 5 patients.

The overall response rate for patients treated in the first line was 69%, and the combined overall response and stable-disease rates were 94%. Among patients treated in the second line, the respective rates were 25% and 79%.

Median overall survival (OS) from the time of the first chemotherapy dose was 16.8 months among the first-line patients vs. 7.9 months among second-line patients (P = .0110)

At the data cutoff, median OS had not been reached for the two highest peptide dose levels (100 and 300 mcg).

The investigators also found that OS was independent of general immune status among the patients, suggesting that the benefit was derived specifically from induced T-cell responses.

‘Provocative and promising’

Invited discussant Heather McArthur, MD, MPH, from Cedars-Sinai Medical Center, Los Angeles, called the finding “provocative and promising.”

Neil Osterweil/Frontline Medical News

AMSTERDAM – Patients with metastatic renal cell carcinoma (mRCC) who experience disease progression in one or more metastatic sites while on treatment with a targeted therapy may still benefit from staying on the same drug rather than switching to another following locoregional treatment, results of a retrospective study suggest.

Among 55 patients with RCC, those who continued on the same targeted therapy after locoregional treatment of a site of progression had significantly longer post–first oligoprogression overall survival (PFOPOS) than patients who had been switched to another targeted agent, reported Della De Lisi, MD, from the University of Rome and colleagues.

“Locoregional treatments represent an option for oligometastatic mRCC treated with targeted therapy. Continuing the same systemic treatment after radical locoregional treatment in one or more metastatic site[s] appear[s] to be an independent predictive factor of better outcome in this subset of patients. Bone oligoprogressive mRCC showed similar better outcome[s].” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

One option for patients with mRCC with slow or limited metastatic progression is locoregional therapy with radical intent, with the goal of achieving a complete response. When a patient’s disease progresses while on a targeted agent such as sorafenib (Nexavar) or sunitinib(Sutent), he or she may be switched to a different agent, but there is a lack of data on outcomes with this strategy, the authors said.

To see whether sticking with the same therapy or switching to another could be the wiser course, they took a retrospective look at outcomes for 55 patients with mRCC who had disease progression after at least 6 months of a first-line therapy in one or more sites treated radically with locoregional therapy.

The majority of patients (52 of 55; 94.5%) had clear-cell histology tumors. Slightly more than half (31 patients, 56.4%) had good risk disease according to the Memorial Sloan Kettering Cancer Center kidney cancer risk prediction tool, and 23 (41.8%) had intermediate risk. The risk category was not calculable for the one remaining patient.

In all, 36 patients (65.5%) did not have evidence of metastasis at diagnosis. All patients had oligoprogression in a single site. The most common metastatic sites were to lung in 15 patients, bone in 10, kidney in 8, brain in 4, and liver in 4 (other sites not listed).

Forty-eight patients received sunitinib in the first line, five received pazopanib (Votrient), and two received sorafenib. Locoregional therapy at the site of progression was radiotherapy in 25 patients (45.5%), surgery in 25, and cryoablation or thermoablation in 5.

The majority of patients (48; 83.6%) remained on the same tyrosine kinase inhibitor (TKI) after locoregional therapy, while 7 were switched to another agent. Of this latter group, four patients were switched to a different TKI, and three were started on a mammalian target of rapamycin (mTOR) inhibitor.

For all patients, the median PFOPOS was 37 months. However, comparing patients who continued the same therapy after locoregional treatment with those who switched, the investigators found a significant survival advantage to sticking with the same therapy, with a median PFOPOS of 39 months, compared with 11 months for patients who were switched to another agent (P = .014)

Other factors contributing to improved survival were good vs. intermediate risk score (39 vs. 29 months; P = .036), metastases to bone vs. viscera (median PFOPOS not reached, vs. 31 months; P = .045), and Fuhrman grade 1 and 2 vs. grade 3 and 4 (57 vs. 37 months; P = .021).

Switching therapies after first progression was an independent risk factor for poor prognosis in a multivariate analysis (hazard ratio 6.280, P = .007).

An analysis of progression-free survival (PFS) after first oligoprogression showed an overall PFS of 14 months. There were no statistically significant differences in terms of post-progression PFS between patients who stayed on the same therapy or were switched, however (15 vs. 7 months, P = .207).

The study was sponsored by participating institutions. The authors reported no conflicts of interest.

AMSTERDAM – Patients with metastatic renal cell carcinoma (mRCC) who experience disease progression in one or more metastatic sites while on treatment with a targeted therapy may still benefit from staying on the same drug rather than switching to another following locoregional treatment, results of a retrospective study suggest.

Among 55 patients with RCC, those who continued on the same targeted therapy after locoregional treatment of a site of progression had significantly longer post–first oligoprogression overall survival (PFOPOS) than patients who had been switched to another targeted agent, reported Della De Lisi, MD, from the University of Rome and colleagues.

“Locoregional treatments represent an option for oligometastatic mRCC treated with targeted therapy. Continuing the same systemic treatment after radical locoregional treatment in one or more metastatic site[s] appear[s] to be an independent predictive factor of better outcome in this subset of patients. Bone oligoprogressive mRCC showed similar better outcome[s].” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

One option for patients with mRCC with slow or limited metastatic progression is locoregional therapy with radical intent, with the goal of achieving a complete response. When a patient’s disease progresses while on a targeted agent such as sorafenib (Nexavar) or sunitinib(Sutent), he or she may be switched to a different agent, but there is a lack of data on outcomes with this strategy, the authors said.

To see whether sticking with the same therapy or switching to another could be the wiser course, they took a retrospective look at outcomes for 55 patients with mRCC who had disease progression after at least 6 months of a first-line therapy in one or more sites treated radically with locoregional therapy.

The majority of patients (52 of 55; 94.5%) had clear-cell histology tumors. Slightly more than half (31 patients, 56.4%) had good risk disease according to the Memorial Sloan Kettering Cancer Center kidney cancer risk prediction tool, and 23 (41.8%) had intermediate risk. The risk category was not calculable for the one remaining patient.

In all, 36 patients (65.5%) did not have evidence of metastasis at diagnosis. All patients had oligoprogression in a single site. The most common metastatic sites were to lung in 15 patients, bone in 10, kidney in 8, brain in 4, and liver in 4 (other sites not listed).

Forty-eight patients received sunitinib in the first line, five received pazopanib (Votrient), and two received sorafenib. Locoregional therapy at the site of progression was radiotherapy in 25 patients (45.5%), surgery in 25, and cryoablation or thermoablation in 5.

The majority of patients (48; 83.6%) remained on the same tyrosine kinase inhibitor (TKI) after locoregional therapy, while 7 were switched to another agent. Of this latter group, four patients were switched to a different TKI, and three were started on a mammalian target of rapamycin (mTOR) inhibitor.

For all patients, the median PFOPOS was 37 months. However, comparing patients who continued the same therapy after locoregional treatment with those who switched, the investigators found a significant survival advantage to sticking with the same therapy, with a median PFOPOS of 39 months, compared with 11 months for patients who were switched to another agent (P = .014)

Other factors contributing to improved survival were good vs. intermediate risk score (39 vs. 29 months; P = .036), metastases to bone vs. viscera (median PFOPOS not reached, vs. 31 months; P = .045), and Fuhrman grade 1 and 2 vs. grade 3 and 4 (57 vs. 37 months; P = .021).

Switching therapies after first progression was an independent risk factor for poor prognosis in a multivariate analysis (hazard ratio 6.280, P = .007).

An analysis of progression-free survival (PFS) after first oligoprogression showed an overall PFS of 14 months. There were no statistically significant differences in terms of post-progression PFS between patients who stayed on the same therapy or were switched, however (15 vs. 7 months, P = .207).

The study was sponsored by participating institutions. The authors reported no conflicts of interest.

AMSTERDAM – Patients with metastatic renal cell carcinoma (mRCC) who experience disease progression in one or more metastatic sites while on treatment with a targeted therapy may still benefit from staying on the same drug rather than switching to another following locoregional treatment, results of a retrospective study suggest.

Among 55 patients with RCC, those who continued on the same targeted therapy after locoregional treatment of a site of progression had significantly longer post–first oligoprogression overall survival (PFOPOS) than patients who had been switched to another targeted agent, reported Della De Lisi, MD, from the University of Rome and colleagues.

“Locoregional treatments represent an option for oligometastatic mRCC treated with targeted therapy. Continuing the same systemic treatment after radical locoregional treatment in one or more metastatic site[s] appear[s] to be an independent predictive factor of better outcome in this subset of patients. Bone oligoprogressive mRCC showed similar better outcome[s].” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

One option for patients with mRCC with slow or limited metastatic progression is locoregional therapy with radical intent, with the goal of achieving a complete response. When a patient’s disease progresses while on a targeted agent such as sorafenib (Nexavar) or sunitinib(Sutent), he or she may be switched to a different agent, but there is a lack of data on outcomes with this strategy, the authors said.

To see whether sticking with the same therapy or switching to another could be the wiser course, they took a retrospective look at outcomes for 55 patients with mRCC who had disease progression after at least 6 months of a first-line therapy in one or more sites treated radically with locoregional therapy.

The majority of patients (52 of 55; 94.5%) had clear-cell histology tumors. Slightly more than half (31 patients, 56.4%) had good risk disease according to the Memorial Sloan Kettering Cancer Center kidney cancer risk prediction tool, and 23 (41.8%) had intermediate risk. The risk category was not calculable for the one remaining patient.

In all, 36 patients (65.5%) did not have evidence of metastasis at diagnosis. All patients had oligoprogression in a single site. The most common metastatic sites were to lung in 15 patients, bone in 10, kidney in 8, brain in 4, and liver in 4 (other sites not listed).

Forty-eight patients received sunitinib in the first line, five received pazopanib (Votrient), and two received sorafenib. Locoregional therapy at the site of progression was radiotherapy in 25 patients (45.5%), surgery in 25, and cryoablation or thermoablation in 5.

The majority of patients (48; 83.6%) remained on the same tyrosine kinase inhibitor (TKI) after locoregional therapy, while 7 were switched to another agent. Of this latter group, four patients were switched to a different TKI, and three were started on a mammalian target of rapamycin (mTOR) inhibitor.

For all patients, the median PFOPOS was 37 months. However, comparing patients who continued the same therapy after locoregional treatment with those who switched, the investigators found a significant survival advantage to sticking with the same therapy, with a median PFOPOS of 39 months, compared with 11 months for patients who were switched to another agent (P = .014)

Other factors contributing to improved survival were good vs. intermediate risk score (39 vs. 29 months; P = .036), metastases to bone vs. viscera (median PFOPOS not reached, vs. 31 months; P = .045), and Fuhrman grade 1 and 2 vs. grade 3 and 4 (57 vs. 37 months; P = .021).

Switching therapies after first progression was an independent risk factor for poor prognosis in a multivariate analysis (hazard ratio 6.280, P = .007).

An analysis of progression-free survival (PFS) after first oligoprogression showed an overall PFS of 14 months. There were no statistically significant differences in terms of post-progression PFS between patients who stayed on the same therapy or were switched, however (15 vs. 7 months, P = .207).

The study was sponsored by participating institutions. The authors reported no conflicts of interest.

AMSTERDAM – Among patients with advanced renal cell carcinoma (RCC) with metastases to bone, cabozantinib (Cabometyx) was associated with better survival compared with everolimus (Afinitor), according to a subanalysis of data from the METEOR trial.

After 2 years of follow-up, median progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were significantly better for patients with bone metastases who received cabozantinib compared with those who received everolimus, reported Sergio Bracarda, MD, of Presidio Ospedaliero San Donato, Italy, and his colleagues.

“Cabozantinib is a new treatment option for previously-treated patients with advanced RCC with benefits that are maintained in patients with bone metastases,” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

Previous studies have shown that patients with advanced RCC with bone metastases have generally poor prognosis compared with patients without bone metastases, the authors noted.

As previously reported, the METEOR trial, a randomized phase III study of 658 patients with advanced RCC, showed a significant survival advantage for patients treated with cabozantinib, with a median OS of 21.4 months compared with 16.5 months for patients treated with everolimus, with a hazard ratio (HR) of 0.66 (P = .0003).

In the current sub-analysis, the investigators looked at a subgroup of 142 patients with bone metastases at baseline as seen on CT or MRI. They conducted an exploratory analysis of bone scan response among 162 patients evaluated for bone lesions at baseline by technetium bone scans, and compared the incidence of skeletal-related events (SREs) for 181 patients with a history of SREs, and 477 with no prior SREs. SREs included pathological fractures, spinal cord compression, surgery to bone, and external radiation therapy to bone.

Patients underwent CT or MRI screening every 8 weeks for the first 12 months post randomization, then every 12 weeks thereafter. All patients were screened with technetium bone scans every 18 weeks for the first years, and those patients with bone lesions at baseline were followed with additional scans every 24 weeks.

The authors also looked at serum bone biomarkers, including bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP), and C-terminal cross-linked telopeptides of type I collagen.

The median PFS for patients with bone metastases treated with cabozantinib was 7.4 months, compared with 2.7 months for everolimus (HR 0.33, 95% confidence interval [CI] 0.21-0.51). For patients with both bone and visceral metastasis, median PFS was 5.6 months vs. 1.9 months, respectively (HR 0.26, 95% CI, 0.16-0.43).

Median OS for the cabozantinib group was 20.1 months compared with 12.1 months for everolimus (HR 0.54, 95% CI, 0.34-0.84) for patients with bone metastases alone. For patients with both bone and visceral metastases, median OS was 20.1 months with cabozantinib, and 10.7 months with everolimus (HR 0.45, 95% CI, 0.28-0.72).

The ORR with cabozantinib as rated by an independent radiology committee was 17% for patients with bone metastases alone, and 20% for patients with bone and visceral metastases. In contrast, there were no objective responses seen in patients treated with everolimus.

Bone scan responses, defined as a 30% or greater decrease from baseline in bone scan lesion area, were seen in 18% of patients on cabozantinib vs. 10% with everolimus (significance not shown).

Among patients with a history of SREs, 22% had an SRE on cabozantinib, compared with 31% on everolimus. Respective rates among patients without a prior history of SREs were 27% and 15%. At least one SRE occurred in 12% (cabo) and 14% (eve) of patients, including four (cabo) and eight (eve) cases of spinal cord compression. For patients with a history of SREs at randomization, the incidence of postrandomization SREs was 16% (cabo) and 34% (eve) and included zero (cabo) and five (eve) cases of spinal cord compression. Reductions in the bone markers P1NP and CTx were greater with cabo vs. eve. The most common adverse events in patients with bone metastases were consistent with those observed in the overall study population.

The investigators noted that “the safety profile of cabozantinib in the bone metastases subgroup was consistent with the safety profile in the overall population.”

Dr. Bracarda has served as a consultant to Exelixis, which supported the trial and subanalysis. Two coauthors are employees of the company.

AMSTERDAM – Among patients with advanced renal cell carcinoma (RCC) with metastases to bone, cabozantinib (Cabometyx) was associated with better survival compared with everolimus (Afinitor), according to a subanalysis of data from the METEOR trial.

After 2 years of follow-up, median progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were significantly better for patients with bone metastases who received cabozantinib compared with those who received everolimus, reported Sergio Bracarda, MD, of Presidio Ospedaliero San Donato, Italy, and his colleagues.

“Cabozantinib is a new treatment option for previously-treated patients with advanced RCC with benefits that are maintained in patients with bone metastases,” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

Previous studies have shown that patients with advanced RCC with bone metastases have generally poor prognosis compared with patients without bone metastases, the authors noted.

As previously reported, the METEOR trial, a randomized phase III study of 658 patients with advanced RCC, showed a significant survival advantage for patients treated with cabozantinib, with a median OS of 21.4 months compared with 16.5 months for patients treated with everolimus, with a hazard ratio (HR) of 0.66 (P = .0003).

In the current sub-analysis, the investigators looked at a subgroup of 142 patients with bone metastases at baseline as seen on CT or MRI. They conducted an exploratory analysis of bone scan response among 162 patients evaluated for bone lesions at baseline by technetium bone scans, and compared the incidence of skeletal-related events (SREs) for 181 patients with a history of SREs, and 477 with no prior SREs. SREs included pathological fractures, spinal cord compression, surgery to bone, and external radiation therapy to bone.

Patients underwent CT or MRI screening every 8 weeks for the first 12 months post randomization, then every 12 weeks thereafter. All patients were screened with technetium bone scans every 18 weeks for the first years, and those patients with bone lesions at baseline were followed with additional scans every 24 weeks.

The authors also looked at serum bone biomarkers, including bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP), and C-terminal cross-linked telopeptides of type I collagen.

The median PFS for patients with bone metastases treated with cabozantinib was 7.4 months, compared with 2.7 months for everolimus (HR 0.33, 95% confidence interval [CI] 0.21-0.51). For patients with both bone and visceral metastasis, median PFS was 5.6 months vs. 1.9 months, respectively (HR 0.26, 95% CI, 0.16-0.43).

Median OS for the cabozantinib group was 20.1 months compared with 12.1 months for everolimus (HR 0.54, 95% CI, 0.34-0.84) for patients with bone metastases alone. For patients with both bone and visceral metastases, median OS was 20.1 months with cabozantinib, and 10.7 months with everolimus (HR 0.45, 95% CI, 0.28-0.72).

The ORR with cabozantinib as rated by an independent radiology committee was 17% for patients with bone metastases alone, and 20% for patients with bone and visceral metastases. In contrast, there were no objective responses seen in patients treated with everolimus.

Bone scan responses, defined as a 30% or greater decrease from baseline in bone scan lesion area, were seen in 18% of patients on cabozantinib vs. 10% with everolimus (significance not shown).

Among patients with a history of SREs, 22% had an SRE on cabozantinib, compared with 31% on everolimus. Respective rates among patients without a prior history of SREs were 27% and 15%. At least one SRE occurred in 12% (cabo) and 14% (eve) of patients, including four (cabo) and eight (eve) cases of spinal cord compression. For patients with a history of SREs at randomization, the incidence of postrandomization SREs was 16% (cabo) and 34% (eve) and included zero (cabo) and five (eve) cases of spinal cord compression. Reductions in the bone markers P1NP and CTx were greater with cabo vs. eve. The most common adverse events in patients with bone metastases were consistent with those observed in the overall study population.

The investigators noted that “the safety profile of cabozantinib in the bone metastases subgroup was consistent with the safety profile in the overall population.”

Dr. Bracarda has served as a consultant to Exelixis, which supported the trial and subanalysis. Two coauthors are employees of the company.

AMSTERDAM – Among patients with advanced renal cell carcinoma (RCC) with metastases to bone, cabozantinib (Cabometyx) was associated with better survival compared with everolimus (Afinitor), according to a subanalysis of data from the METEOR trial.

After 2 years of follow-up, median progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were significantly better for patients with bone metastases who received cabozantinib compared with those who received everolimus, reported Sergio Bracarda, MD, of Presidio Ospedaliero San Donato, Italy, and his colleagues.

“Cabozantinib is a new treatment option for previously-treated patients with advanced RCC with benefits that are maintained in patients with bone metastases,” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

Previous studies have shown that patients with advanced RCC with bone metastases have generally poor prognosis compared with patients without bone metastases, the authors noted.

As previously reported, the METEOR trial, a randomized phase III study of 658 patients with advanced RCC, showed a significant survival advantage for patients treated with cabozantinib, with a median OS of 21.4 months compared with 16.5 months for patients treated with everolimus, with a hazard ratio (HR) of 0.66 (P = .0003).

In the current sub-analysis, the investigators looked at a subgroup of 142 patients with bone metastases at baseline as seen on CT or MRI. They conducted an exploratory analysis of bone scan response among 162 patients evaluated for bone lesions at baseline by technetium bone scans, and compared the incidence of skeletal-related events (SREs) for 181 patients with a history of SREs, and 477 with no prior SREs. SREs included pathological fractures, spinal cord compression, surgery to bone, and external radiation therapy to bone.

Patients underwent CT or MRI screening every 8 weeks for the first 12 months post randomization, then every 12 weeks thereafter. All patients were screened with technetium bone scans every 18 weeks for the first years, and those patients with bone lesions at baseline were followed with additional scans every 24 weeks.

The authors also looked at serum bone biomarkers, including bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP), and C-terminal cross-linked telopeptides of type I collagen.

The median PFS for patients with bone metastases treated with cabozantinib was 7.4 months, compared with 2.7 months for everolimus (HR 0.33, 95% confidence interval [CI] 0.21-0.51). For patients with both bone and visceral metastasis, median PFS was 5.6 months vs. 1.9 months, respectively (HR 0.26, 95% CI, 0.16-0.43).

Median OS for the cabozantinib group was 20.1 months compared with 12.1 months for everolimus (HR 0.54, 95% CI, 0.34-0.84) for patients with bone metastases alone. For patients with both bone and visceral metastases, median OS was 20.1 months with cabozantinib, and 10.7 months with everolimus (HR 0.45, 95% CI, 0.28-0.72).

The ORR with cabozantinib as rated by an independent radiology committee was 17% for patients with bone metastases alone, and 20% for patients with bone and visceral metastases. In contrast, there were no objective responses seen in patients treated with everolimus.

Bone scan responses, defined as a 30% or greater decrease from baseline in bone scan lesion area, were seen in 18% of patients on cabozantinib vs. 10% with everolimus (significance not shown).

Among patients with a history of SREs, 22% had an SRE on cabozantinib, compared with 31% on everolimus. Respective rates among patients without a prior history of SREs were 27% and 15%. At least one SRE occurred in 12% (cabo) and 14% (eve) of patients, including four (cabo) and eight (eve) cases of spinal cord compression. For patients with a history of SREs at randomization, the incidence of postrandomization SREs was 16% (cabo) and 34% (eve) and included zero (cabo) and five (eve) cases of spinal cord compression. Reductions in the bone markers P1NP and CTx were greater with cabo vs. eve. The most common adverse events in patients with bone metastases were consistent with those observed in the overall study population.

The investigators noted that “the safety profile of cabozantinib in the bone metastases subgroup was consistent with the safety profile in the overall population.”

Dr. Bracarda has served as a consultant to Exelixis, which supported the trial and subanalysis. Two coauthors are employees of the company.

AMSTERDAM – Pathological fractures are prognostic of poor outcomes in adults with osteosarcoma, but not in children with osteosarcoma, investigators have found.

A retrospective review of data on consecutive patients treated over the course of 30 years showed that among patients of all ages, both 5-year and 10-year overall survival (OS) rates were worse among patients who had pathological fractures.

But in an analysis stratified by age, the survival difference attributable to fractures was limited entirely to patients who were 18 or older at the time of an osteosarcoma diagnosis, reported Lisa Kelley, a medical student at the Ludwig-Maximilians Universität in Munich.

AMSTERDAM – Pathological fractures are prognostic of poor outcomes in adults with osteosarcoma, but not in children with osteosarcoma, investigators have found.

A retrospective review of data on consecutive patients treated over the course of 30 years showed that among patients of all ages, both 5-year and 10-year overall survival (OS) rates were worse among patients who had pathological fractures.

But in an analysis stratified by age, the survival difference attributable to fractures was limited entirely to patients who were 18 or older at the time of an osteosarcoma diagnosis, reported Lisa Kelley, a medical student at the Ludwig-Maximilians Universität in Munich.

AMSTERDAM – Pathological fractures are prognostic of poor outcomes in adults with osteosarcoma, but not in children with osteosarcoma, investigators have found.

A retrospective review of data on consecutive patients treated over the course of 30 years showed that among patients of all ages, both 5-year and 10-year overall survival (OS) rates were worse among patients who had pathological fractures.

But in an analysis stratified by age, the survival difference attributable to fractures was limited entirely to patients who were 18 or older at the time of an osteosarcoma diagnosis, reported Lisa Kelley, a medical student at the Ludwig-Maximilians Universität in Munich.

AMSTERDAM – Immune checkpoint inhibitors targeted against programmed death–1 (PD-1) and its ligand (PD-L1) show strong activity against several different tumor types, but unfortunately may have only limited efficacy against soft tissue and bone sarcomas, investigators reported.

“We found that the clinical expression of PD-1, PD-L1, and CD8 is sarcoma subtype dependent,” said Anke van Erp, a PhD candidate in oncology at Radboud University Medical Center in Nijmegen, the Netherlands.

op@frontlinemedcom.com

AMSTERDAM – Immune checkpoint inhibitors targeted against programmed death–1 (PD-1) and its ligand (PD-L1) show strong activity against several different tumor types, but unfortunately may have only limited efficacy against soft tissue and bone sarcomas, investigators reported.

“We found that the clinical expression of PD-1, PD-L1, and CD8 is sarcoma subtype dependent,” said Anke van Erp, a PhD candidate in oncology at Radboud University Medical Center in Nijmegen, the Netherlands.

op@frontlinemedcom.com

AMSTERDAM – Immune checkpoint inhibitors targeted against programmed death–1 (PD-1) and its ligand (PD-L1) show strong activity against several different tumor types, but unfortunately may have only limited efficacy against soft tissue and bone sarcomas, investigators reported.

“We found that the clinical expression of PD-1, PD-L1, and CD8 is sarcoma subtype dependent,” said Anke van Erp, a PhD candidate in oncology at Radboud University Medical Center in Nijmegen, the Netherlands.

op@frontlinemedcom.com

AMSTERDAM – Incretin-based antidiabetic drugs do not appear to increase risk for pancreatic cancer, but the acute need for these drugs because of rapid worsening of type 2 diabetes may be a marker for early, occult pancreatic adenocarcinoma, investigators cautioned.

Results of a study of nearly 825,000 patients with type 2 diabetes in Belgium and northern Italy showed that patients who required a first-time prescription for an incretin-based antidiabetic drug had a 3.5-fold greater risk of being diagnosed with pancreatic cancer within 3 months, compared with patients who could be safely maintained on an oral noninsulin, nonincretin antidiabetic drug (NIAD), reported Alice Koechlin of the International Prevention Research Institute in Lyon, France, on behalf of coauthor Phillipe Autier, MD, also of the institute.

op@frontlinemedcom.com

AMSTERDAM – Incretin-based antidiabetic drugs do not appear to increase risk for pancreatic cancer, but the acute need for these drugs because of rapid worsening of type 2 diabetes may be a marker for early, occult pancreatic adenocarcinoma, investigators cautioned.

Results of a study of nearly 825,000 patients with type 2 diabetes in Belgium and northern Italy showed that patients who required a first-time prescription for an incretin-based antidiabetic drug had a 3.5-fold greater risk of being diagnosed with pancreatic cancer within 3 months, compared with patients who could be safely maintained on an oral noninsulin, nonincretin antidiabetic drug (NIAD), reported Alice Koechlin of the International Prevention Research Institute in Lyon, France, on behalf of coauthor Phillipe Autier, MD, also of the institute.

op@frontlinemedcom.com

AMSTERDAM – Incretin-based antidiabetic drugs do not appear to increase risk for pancreatic cancer, but the acute need for these drugs because of rapid worsening of type 2 diabetes may be a marker for early, occult pancreatic adenocarcinoma, investigators cautioned.

Results of a study of nearly 825,000 patients with type 2 diabetes in Belgium and northern Italy showed that patients who required a first-time prescription for an incretin-based antidiabetic drug had a 3.5-fold greater risk of being diagnosed with pancreatic cancer within 3 months, compared with patients who could be safely maintained on an oral noninsulin, nonincretin antidiabetic drug (NIAD), reported Alice Koechlin of the International Prevention Research Institute in Lyon, France, on behalf of coauthor Phillipe Autier, MD, also of the institute.

op@frontlinemedcom.com

AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.

“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.

Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.

Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.

imnews@frontlinemedcom.com

AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.

“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.

Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.

Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.

imnews@frontlinemedcom.com

AMSTERDAM – Five years after a cancer diagnosis, patients who report having chronic neuropathic pain are twice as likely to be out of work as patients who report having no neuropathic pain, authors of a large longitudinal study said.

“For middle-term cancer survivors, suffering from chronic neuropathic pain unfortunately predicts labor-market exit,” said Marc-Karim Bendiane, from Aix-Marseille University in Marseille, France.

Pain is still frequently underdiagnosed, poorly managed, and undertreated among cancer survivors, and there is a need for alternatives to analgesics for control of chronic neuropathic pain (CNP), Mr. Bendiane said at an annual congress sponsored by the European Cancer Organisation.

Mr. Bendiane and colleagues used data from VICAN, a longitudinal survey of issues of concern to cancer survivors 2 years and 5 years after a diagnosis. The cohort consists of patients diagnosed with cancers who comprise 88% of all cancer diagnoses in France, including cancers of the breast; colon and rectum; lip, oral cavity, and pharynx; kidney; cervix; endometrium; non-Hodgkin lymphoma; melanoma; thyroid; bladder; and prostate.

imnews@frontlinemedcom.com

AMSTERDAM – Analyses of patient-reported outcomes in the UK START A and B trials show that radiation doses greater than 2 Gy to the supraclavicular fossa or axilla are safe and are associated with acceptable near- and late-term toxicities, trial investigators reported.

The START trials compared standard adjuvant radiation doses and schedules with accelerated, hypofractionated doses in women with early breast cancer.

At the annual San Antonio Breast Cancer Symposium in 2012, lead investigator John Yarnold, MD, professor of clinical oncology at the Institute of Cancer Research in London, reported that a 40-Gy, 15-fraction regimen was associated with fewer adverse events over 10 years of follow-up compared with a 50-Gy, 25-fraction regimen that was at the time the standard in the United States and the United Kingdom.

Here at an annual congress sponsored by the European Cancer Organisation, Dr. Yarnold reported that among 479 patients in the two trials who had lymphatic radiation, there were no significant differences in arm or shoulder pain, swelling, motion problems, or shoulder stiffness between patients who received conventional 2-Gy fractions for a total of 50 Gy, or lower total doses of radiation divided into fractions larger than 2 Gy.

“A post hoc analysis of outcomes in 479 patients treated with radiotherapy fractions larger than 2 Gy to the supraclavicular fossa and/or the axilla raise no concerns in terms of safety or patient acceptability, and it was for this reason that this schedule has been the standard for locoregional radiotherapy in the UK for some years now,” he said.

START (Standardization of Breast Radiotherapy) A enrolled 2,236 patients from 35 UK centers with breast cancer stages T 1-3, nodal stage N0-1, and no distant metastases (M0) and randomly assigned them to 50 Gy in 25 fractions of 2 Gy each over 5 weeks, 39.0 Gy in 13 fractions of 3.0 Gy over 5 weeks, and 41.6 Gy in 13 fractions of 3.2 Gy over 5 weeks.

In START B, 2,215 women were randomly assigned to the 50 Gy or 40 Gy regimens.

As reported in 2012, over a median follow-up of 9.3 years in START A, the 41.6-Gy regimen was similar in its adverse events profile compared with the 50-Gy dose (hazard ratio [HR] 0.94, and the lower-dose regimen also was comparable in efficacy, as measured by the rate of locoregional tumor relapse.

There were numerically but not significantly more relapses in the 39-Gy dose, however.

In START B, the 40-Gy dose was associated with significantly fewer adverse events over a median of 9.9 years of follow-up (HR 0.77). Efficacy was similar, although there was a nonsignificant trend toward superiority for the hypofractionated regimen.

In the post hoc analysis, the investigators looked at adverse events in 479 total patients in START A and B, 365 of whom had completed patient-reported outcome measures on the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer–Specific Quality of Life Questionnaire (QLQ-BR23).

A total of 262 patients in START A, and 103 in START B completed the questionnaires at 0, 6, 12, 24, and 60 months. Of these patients. The majority in each arm had radiation to the supraclavicular fossa only, and a minority had axilla radiation alone or in addition to supraclavicular fossa radiation.

In START B, 5-year patient reported outcomes of severity of 3 or 4 on a 4-point scale were low in each treatment arm, with arm or hand swelling reported in 10% of patients on 50 Gy, and 6% of patients on 40 Gy, and shoulder stiffness reported in 12% on the 50-Gy dose, vs. 15% on the 40-Gy dose.

Among all 479 patients with clinical assessments at 10 years, there were also no significant differences in either arm edema or shoulder stiffness between patients who received 50 Gy and those who received other, hypofractionated in each of the two trials.

The findings lend support to the Danish Breast Cancer Cooperative Group’s SKAGEN Trial 1, which is evaluating moderately hypofractionated locoregional adjuvant radiation therapy of early breast cancer combined with a simultaneous integrated boost in patients with an indication for boost, Dr. Yarnold said.

The UK START trials were supported by Cancer Research UK, the Medical Research Council, and the National Cancer Research Institute. Dr. Yarnold reported having no conflicts of interest.

AMSTERDAM – Analyses of patient-reported outcomes in the UK START A and B trials show that radiation doses greater than 2 Gy to the supraclavicular fossa or axilla are safe and are associated with acceptable near- and late-term toxicities, trial investigators reported.

The START trials compared standard adjuvant radiation doses and schedules with accelerated, hypofractionated doses in women with early breast cancer.

At the annual San Antonio Breast Cancer Symposium in 2012, lead investigator John Yarnold, MD, professor of clinical oncology at the Institute of Cancer Research in London, reported that a 40-Gy, 15-fraction regimen was associated with fewer adverse events over 10 years of follow-up compared with a 50-Gy, 25-fraction regimen that was at the time the standard in the United States and the United Kingdom.

Here at an annual congress sponsored by the European Cancer Organisation, Dr. Yarnold reported that among 479 patients in the two trials who had lymphatic radiation, there were no significant differences in arm or shoulder pain, swelling, motion problems, or shoulder stiffness between patients who received conventional 2-Gy fractions for a total of 50 Gy, or lower total doses of radiation divided into fractions larger than 2 Gy.

“A post hoc analysis of outcomes in 479 patients treated with radiotherapy fractions larger than 2 Gy to the supraclavicular fossa and/or the axilla raise no concerns in terms of safety or patient acceptability, and it was for this reason that this schedule has been the standard for locoregional radiotherapy in the UK for some years now,” he said.

START (Standardization of Breast Radiotherapy) A enrolled 2,236 patients from 35 UK centers with breast cancer stages T 1-3, nodal stage N0-1, and no distant metastases (M0) and randomly assigned them to 50 Gy in 25 fractions of 2 Gy each over 5 weeks, 39.0 Gy in 13 fractions of 3.0 Gy over 5 weeks, and 41.6 Gy in 13 fractions of 3.2 Gy over 5 weeks.

In START B, 2,215 women were randomly assigned to the 50 Gy or 40 Gy regimens.

As reported in 2012, over a median follow-up of 9.3 years in START A, the 41.6-Gy regimen was similar in its adverse events profile compared with the 50-Gy dose (hazard ratio [HR] 0.94, and the lower-dose regimen also was comparable in efficacy, as measured by the rate of locoregional tumor relapse.

There were numerically but not significantly more relapses in the 39-Gy dose, however.

In START B, the 40-Gy dose was associated with significantly fewer adverse events over a median of 9.9 years of follow-up (HR 0.77). Efficacy was similar, although there was a nonsignificant trend toward superiority for the hypofractionated regimen.

In the post hoc analysis, the investigators looked at adverse events in 479 total patients in START A and B, 365 of whom had completed patient-reported outcome measures on the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer–Specific Quality of Life Questionnaire (QLQ-BR23).

A total of 262 patients in START A, and 103 in START B completed the questionnaires at 0, 6, 12, 24, and 60 months. Of these patients. The majority in each arm had radiation to the supraclavicular fossa only, and a minority had axilla radiation alone or in addition to supraclavicular fossa radiation.

In START B, 5-year patient reported outcomes of severity of 3 or 4 on a 4-point scale were low in each treatment arm, with arm or hand swelling reported in 10% of patients on 50 Gy, and 6% of patients on 40 Gy, and shoulder stiffness reported in 12% on the 50-Gy dose, vs. 15% on the 40-Gy dose.

Among all 479 patients with clinical assessments at 10 years, there were also no significant differences in either arm edema or shoulder stiffness between patients who received 50 Gy and those who received other, hypofractionated in each of the two trials.

The findings lend support to the Danish Breast Cancer Cooperative Group’s SKAGEN Trial 1, which is evaluating moderately hypofractionated locoregional adjuvant radiation therapy of early breast cancer combined with a simultaneous integrated boost in patients with an indication for boost, Dr. Yarnold said.

The UK START trials were supported by Cancer Research UK, the Medical Research Council, and the National Cancer Research Institute. Dr. Yarnold reported having no conflicts of interest.

AMSTERDAM – Analyses of patient-reported outcomes in the UK START A and B trials show that radiation doses greater than 2 Gy to the supraclavicular fossa or axilla are safe and are associated with acceptable near- and late-term toxicities, trial investigators reported.

The START trials compared standard adjuvant radiation doses and schedules with accelerated, hypofractionated doses in women with early breast cancer.

At the annual San Antonio Breast Cancer Symposium in 2012, lead investigator John Yarnold, MD, professor of clinical oncology at the Institute of Cancer Research in London, reported that a 40-Gy, 15-fraction regimen was associated with fewer adverse events over 10 years of follow-up compared with a 50-Gy, 25-fraction regimen that was at the time the standard in the United States and the United Kingdom.

Here at an annual congress sponsored by the European Cancer Organisation, Dr. Yarnold reported that among 479 patients in the two trials who had lymphatic radiation, there were no significant differences in arm or shoulder pain, swelling, motion problems, or shoulder stiffness between patients who received conventional 2-Gy fractions for a total of 50 Gy, or lower total doses of radiation divided into fractions larger than 2 Gy.

“A post hoc analysis of outcomes in 479 patients treated with radiotherapy fractions larger than 2 Gy to the supraclavicular fossa and/or the axilla raise no concerns in terms of safety or patient acceptability, and it was for this reason that this schedule has been the standard for locoregional radiotherapy in the UK for some years now,” he said.

START (Standardization of Breast Radiotherapy) A enrolled 2,236 patients from 35 UK centers with breast cancer stages T 1-3, nodal stage N0-1, and no distant metastases (M0) and randomly assigned them to 50 Gy in 25 fractions of 2 Gy each over 5 weeks, 39.0 Gy in 13 fractions of 3.0 Gy over 5 weeks, and 41.6 Gy in 13 fractions of 3.2 Gy over 5 weeks.

In START B, 2,215 women were randomly assigned to the 50 Gy or 40 Gy regimens.

As reported in 2012, over a median follow-up of 9.3 years in START A, the 41.6-Gy regimen was similar in its adverse events profile compared with the 50-Gy dose (hazard ratio [HR] 0.94, and the lower-dose regimen also was comparable in efficacy, as measured by the rate of locoregional tumor relapse.

There were numerically but not significantly more relapses in the 39-Gy dose, however.

In START B, the 40-Gy dose was associated with significantly fewer adverse events over a median of 9.9 years of follow-up (HR 0.77). Efficacy was similar, although there was a nonsignificant trend toward superiority for the hypofractionated regimen.

In the post hoc analysis, the investigators looked at adverse events in 479 total patients in START A and B, 365 of whom had completed patient-reported outcome measures on the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer–Specific Quality of Life Questionnaire (QLQ-BR23).

A total of 262 patients in START A, and 103 in START B completed the questionnaires at 0, 6, 12, 24, and 60 months. Of these patients. The majority in each arm had radiation to the supraclavicular fossa only, and a minority had axilla radiation alone or in addition to supraclavicular fossa radiation.

In START B, 5-year patient reported outcomes of severity of 3 or 4 on a 4-point scale were low in each treatment arm, with arm or hand swelling reported in 10% of patients on 50 Gy, and 6% of patients on 40 Gy, and shoulder stiffness reported in 12% on the 50-Gy dose, vs. 15% on the 40-Gy dose.

Among all 479 patients with clinical assessments at 10 years, there were also no significant differences in either arm edema or shoulder stiffness between patients who received 50 Gy and those who received other, hypofractionated in each of the two trials.

The findings lend support to the Danish Breast Cancer Cooperative Group’s SKAGEN Trial 1, which is evaluating moderately hypofractionated locoregional adjuvant radiation therapy of early breast cancer combined with a simultaneous integrated boost in patients with an indication for boost, Dr. Yarnold said.

The UK START trials were supported by Cancer Research UK, the Medical Research Council, and the National Cancer Research Institute. Dr. Yarnold reported having no conflicts of interest.

AMSTERDAM – In real-life practice, women with early, localized breast cancer who underwent breast conserving therapy had better breast cancer–specific and overall survival compared with women who underwent mastectomy, according to investigators in the Netherlands.

Among nearly 130,000 patients treated over two different time periods, breast-conserving surgery and radiation (BCT) was associated with superior survival for women older than 50, patients who did not receive adjuvant chemotherapy, and those with comorbidities – irrespective of either hormonal or human epidermal growth factor receptor 2 (HER2) status, reported Mirelle Lagendijk, MD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands.

AMSTERDAM – In real-life practice, women with early, localized breast cancer who underwent breast conserving therapy had better breast cancer–specific and overall survival compared with women who underwent mastectomy, according to investigators in the Netherlands.

Among nearly 130,000 patients treated over two different time periods, breast-conserving surgery and radiation (BCT) was associated with superior survival for women older than 50, patients who did not receive adjuvant chemotherapy, and those with comorbidities – irrespective of either hormonal or human epidermal growth factor receptor 2 (HER2) status, reported Mirelle Lagendijk, MD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands.

AMSTERDAM – In real-life practice, women with early, localized breast cancer who underwent breast conserving therapy had better breast cancer–specific and overall survival compared with women who underwent mastectomy, according to investigators in the Netherlands.

Among nearly 130,000 patients treated over two different time periods, breast-conserving surgery and radiation (BCT) was associated with superior survival for women older than 50, patients who did not receive adjuvant chemotherapy, and those with comorbidities – irrespective of either hormonal or human epidermal growth factor receptor 2 (HER2) status, reported Mirelle Lagendijk, MD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands.