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RCC research has opened door to the future, but “much work remains to be done”
Recent research on the genetic basis of renal cell carcinoma has expanded and improved treatment options; however, personalized medicine is still largely unavailable, so future efforts should aim to link genetic knowledge with prognosis and treatment selection, according to the authors of a recent review article.
The article, written by Christopher D’Avella, MD, of the Fox Chase Cancer Center in Philadelphia, and his colleagues provides an overview of renal cell carcinoma (RCC) mutations and associated therapies, with updates of ongoing trials and a look at future directions.
“The expansion of treatment options for patients with advanced RCC over the past 15 years is a testament to enhanced understanding of the genetics and genomics of RCC and the ability to apply this knowledge to drug development,” the authors wrote in Urologic Oncology. “However, much work remains to be done as there are still no validated biomarkers to select patient treatment, and in only rare cases, the knowledge of particular mutations in RCC can lead to rational treatment selection.”
RCC accounts for approximately 80%-85% of renal tumors. About three out of four RCC patients have clear cell disease, of which about 30% develop metastases and need systemic therapy. The authors pointed out that vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been standard first-line care for these patients since the mid-2000s, based on improved molecular understanding. Still, responses to TKIs are limited and patients eventually develop resistance. Several agents are in development to overcome this obstacle, including inhibitors of hypoxia inducible factor, which have recently shown promise. Among biomarkers for ccRCC, PBRM1 mutations may be associated with susceptibility to checkpoint inhibitors, and TSC1 could predict response to mTOR (mammalian target of rapamycin) inhibition.
Along with clear cell RCC, the review article addressed topics in papillary and sarcomatoid subtypes.
Patients with papillary RCC often have MET mutations, and ongoing research is focused on associated targeted therapies. For example, savolitinib is a highly selective MET inhibitor that has shown promise in this patient subgroup.
Sarcomatoid features remain characteristic of large and aggressive tumors. Unfortunately, treatment options are currently limited in this area. Recent studies suggest that TP53 and NF2 mutations are associated with sarcomatoid differentiation.
“Future studies should explore linking genetics to prognosis, resistance to targeted therapies, and the identification of future therapeutic targets,” the authors concluded.
SOURCE: D’Avella C et al. Urol Oncol. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.10.027.
Recent research on the genetic basis of renal cell carcinoma has expanded and improved treatment options; however, personalized medicine is still largely unavailable, so future efforts should aim to link genetic knowledge with prognosis and treatment selection, according to the authors of a recent review article.
The article, written by Christopher D’Avella, MD, of the Fox Chase Cancer Center in Philadelphia, and his colleagues provides an overview of renal cell carcinoma (RCC) mutations and associated therapies, with updates of ongoing trials and a look at future directions.
“The expansion of treatment options for patients with advanced RCC over the past 15 years is a testament to enhanced understanding of the genetics and genomics of RCC and the ability to apply this knowledge to drug development,” the authors wrote in Urologic Oncology. “However, much work remains to be done as there are still no validated biomarkers to select patient treatment, and in only rare cases, the knowledge of particular mutations in RCC can lead to rational treatment selection.”
RCC accounts for approximately 80%-85% of renal tumors. About three out of four RCC patients have clear cell disease, of which about 30% develop metastases and need systemic therapy. The authors pointed out that vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been standard first-line care for these patients since the mid-2000s, based on improved molecular understanding. Still, responses to TKIs are limited and patients eventually develop resistance. Several agents are in development to overcome this obstacle, including inhibitors of hypoxia inducible factor, which have recently shown promise. Among biomarkers for ccRCC, PBRM1 mutations may be associated with susceptibility to checkpoint inhibitors, and TSC1 could predict response to mTOR (mammalian target of rapamycin) inhibition.
Along with clear cell RCC, the review article addressed topics in papillary and sarcomatoid subtypes.
Patients with papillary RCC often have MET mutations, and ongoing research is focused on associated targeted therapies. For example, savolitinib is a highly selective MET inhibitor that has shown promise in this patient subgroup.
Sarcomatoid features remain characteristic of large and aggressive tumors. Unfortunately, treatment options are currently limited in this area. Recent studies suggest that TP53 and NF2 mutations are associated with sarcomatoid differentiation.
“Future studies should explore linking genetics to prognosis, resistance to targeted therapies, and the identification of future therapeutic targets,” the authors concluded.
SOURCE: D’Avella C et al. Urol Oncol. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.10.027.
Recent research on the genetic basis of renal cell carcinoma has expanded and improved treatment options; however, personalized medicine is still largely unavailable, so future efforts should aim to link genetic knowledge with prognosis and treatment selection, according to the authors of a recent review article.
The article, written by Christopher D’Avella, MD, of the Fox Chase Cancer Center in Philadelphia, and his colleagues provides an overview of renal cell carcinoma (RCC) mutations and associated therapies, with updates of ongoing trials and a look at future directions.
“The expansion of treatment options for patients with advanced RCC over the past 15 years is a testament to enhanced understanding of the genetics and genomics of RCC and the ability to apply this knowledge to drug development,” the authors wrote in Urologic Oncology. “However, much work remains to be done as there are still no validated biomarkers to select patient treatment, and in only rare cases, the knowledge of particular mutations in RCC can lead to rational treatment selection.”
RCC accounts for approximately 80%-85% of renal tumors. About three out of four RCC patients have clear cell disease, of which about 30% develop metastases and need systemic therapy. The authors pointed out that vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been standard first-line care for these patients since the mid-2000s, based on improved molecular understanding. Still, responses to TKIs are limited and patients eventually develop resistance. Several agents are in development to overcome this obstacle, including inhibitors of hypoxia inducible factor, which have recently shown promise. Among biomarkers for ccRCC, PBRM1 mutations may be associated with susceptibility to checkpoint inhibitors, and TSC1 could predict response to mTOR (mammalian target of rapamycin) inhibition.
Along with clear cell RCC, the review article addressed topics in papillary and sarcomatoid subtypes.
Patients with papillary RCC often have MET mutations, and ongoing research is focused on associated targeted therapies. For example, savolitinib is a highly selective MET inhibitor that has shown promise in this patient subgroup.
Sarcomatoid features remain characteristic of large and aggressive tumors. Unfortunately, treatment options are currently limited in this area. Recent studies suggest that TP53 and NF2 mutations are associated with sarcomatoid differentiation.
“Future studies should explore linking genetics to prognosis, resistance to targeted therapies, and the identification of future therapeutic targets,” the authors concluded.
SOURCE: D’Avella C et al. Urol Oncol. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.10.027.
FROM UROLOGIC ONCOLOGY
Key clinical point: Recent research on the genetic basis of renal cell carcinoma has expanded and improved treatment options but personalized medicine is still largely unavailable.
Major finding: There are still no validated biomarkers to select patient treatment, and in only rare cases does the knowledge of particular mutations in renal cell carcinoma lead to rational treatment selection.
Study details: A review article of mutations in renal cell carcinoma and associated treatment options.
Disclosures: This work was supported by the Canadian Cancer Society and the Canadian Institutes of Health.
Source: D’Avella C et al. Urol Oncol. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.10.027.
hTERT expression predicts RCC survival, tumor aggressiveness
Human telomerase reverse transcriptase (hTERT) protein expression is associated with clear cell renal carcinoma (ccRCC) tumor aggressiveness and disease-specific survival (DSS), according to investigators.
Associations between hTERT expression and clinicopathologic features and outcomes were less robust or nonexistent in papillary and chromophobe subtypes, reported Leili Saeednejad Zanjani, MD, of the Oncopathology Research Center at Iran University of Medical Sciences in Tehran, and colleagues.
“Evidence shows that telomerase is expressed in 85% of malignancies, and the level of its activity is higher in advanced and metastatic tumors,” the authors wrote in Pathology.
“A number of clinical studies have been performed to evaluate the association between telomerase activity and clinicopathological parameters in renal cancer showing that telomerase activity level correlates with progression of RCC,” Dr. Zanjani and associates wrote. As none of these specifically evaluated hTERT protein expression, the investigators conducted a study to learn more.
The investigators analyzed hTERT expression level in 176 cases of RCC, requiring that each tumor had three core biopsies because of concerns of heterogeneity. The population consisted of 113 clear cell, 12 type I papillary, 20 type II papillary, and 31 chromophobe subtypes. Patient and clinicopathologic features were compared with survival and hTERT expression. Median follow-up time was 42 months.
Correlations between hTERT expression and disease characteristics were pronounced in cases of ccRCC, compared with other subtypes. In ccRCC, hTERT expression was significantly associated with tumor stage, nucleolar grade, tumor size, microvascular invasion, lymph node invasion, renal pelvis involvement, renal sinus fat involvement, Gerota fascia invasion, and distant metastasis. Survival analysis showed that DSS of ccRCC patients with high hTERT expression was 58 months, compared with 68 months for those with low hTERT expression (P =.012). Other parameters associated with survival were nucleolar grade, tumor stage, and tumor size.
For type I and II papillary subtypes, associations were found between hTERT expression and tumor stage and distant metastasis. In contrast, chromophobe RCC revealed no such relationships. No associations were found between hTERT expression and survival in any of these three latter subtypes, for slightly different reasons; no patients with type I disease died of renal cancer, disallowing creation of a Kaplan-Meier survival curve, whereas type II and chromophobe survival curves revealed insignificant relationships with hTERT expression. Along the same lines, no clinicopathologic characteristics of these subtypes were tied with survival.
“From these findings we are able to conclude that hTERT protein expression may be a novel prognostic indicator of worse outcome in tumor biopsies of patients with ccRCC, if follow up time is more prolonged,” the authors wrote. They noted that “telomerase is an attractive and ideal target for therapy due to overexpression in the majority of malignancies and low or nonexpression in most somatic cells.”
The study was funded by the Iran National Science Foundation. The authors declared no conflicts of interest.
SOURCE: Zanjani LS et al. Pathology. 2018 Nov 19. doi: 10.1016/j.pathol.2018.08.019.
Human telomerase reverse transcriptase (hTERT) protein expression is associated with clear cell renal carcinoma (ccRCC) tumor aggressiveness and disease-specific survival (DSS), according to investigators.
Associations between hTERT expression and clinicopathologic features and outcomes were less robust or nonexistent in papillary and chromophobe subtypes, reported Leili Saeednejad Zanjani, MD, of the Oncopathology Research Center at Iran University of Medical Sciences in Tehran, and colleagues.
“Evidence shows that telomerase is expressed in 85% of malignancies, and the level of its activity is higher in advanced and metastatic tumors,” the authors wrote in Pathology.
“A number of clinical studies have been performed to evaluate the association between telomerase activity and clinicopathological parameters in renal cancer showing that telomerase activity level correlates with progression of RCC,” Dr. Zanjani and associates wrote. As none of these specifically evaluated hTERT protein expression, the investigators conducted a study to learn more.
The investigators analyzed hTERT expression level in 176 cases of RCC, requiring that each tumor had three core biopsies because of concerns of heterogeneity. The population consisted of 113 clear cell, 12 type I papillary, 20 type II papillary, and 31 chromophobe subtypes. Patient and clinicopathologic features were compared with survival and hTERT expression. Median follow-up time was 42 months.
Correlations between hTERT expression and disease characteristics were pronounced in cases of ccRCC, compared with other subtypes. In ccRCC, hTERT expression was significantly associated with tumor stage, nucleolar grade, tumor size, microvascular invasion, lymph node invasion, renal pelvis involvement, renal sinus fat involvement, Gerota fascia invasion, and distant metastasis. Survival analysis showed that DSS of ccRCC patients with high hTERT expression was 58 months, compared with 68 months for those with low hTERT expression (P =.012). Other parameters associated with survival were nucleolar grade, tumor stage, and tumor size.
For type I and II papillary subtypes, associations were found between hTERT expression and tumor stage and distant metastasis. In contrast, chromophobe RCC revealed no such relationships. No associations were found between hTERT expression and survival in any of these three latter subtypes, for slightly different reasons; no patients with type I disease died of renal cancer, disallowing creation of a Kaplan-Meier survival curve, whereas type II and chromophobe survival curves revealed insignificant relationships with hTERT expression. Along the same lines, no clinicopathologic characteristics of these subtypes were tied with survival.
“From these findings we are able to conclude that hTERT protein expression may be a novel prognostic indicator of worse outcome in tumor biopsies of patients with ccRCC, if follow up time is more prolonged,” the authors wrote. They noted that “telomerase is an attractive and ideal target for therapy due to overexpression in the majority of malignancies and low or nonexpression in most somatic cells.”
The study was funded by the Iran National Science Foundation. The authors declared no conflicts of interest.
SOURCE: Zanjani LS et al. Pathology. 2018 Nov 19. doi: 10.1016/j.pathol.2018.08.019.
Human telomerase reverse transcriptase (hTERT) protein expression is associated with clear cell renal carcinoma (ccRCC) tumor aggressiveness and disease-specific survival (DSS), according to investigators.
Associations between hTERT expression and clinicopathologic features and outcomes were less robust or nonexistent in papillary and chromophobe subtypes, reported Leili Saeednejad Zanjani, MD, of the Oncopathology Research Center at Iran University of Medical Sciences in Tehran, and colleagues.
“Evidence shows that telomerase is expressed in 85% of malignancies, and the level of its activity is higher in advanced and metastatic tumors,” the authors wrote in Pathology.
“A number of clinical studies have been performed to evaluate the association between telomerase activity and clinicopathological parameters in renal cancer showing that telomerase activity level correlates with progression of RCC,” Dr. Zanjani and associates wrote. As none of these specifically evaluated hTERT protein expression, the investigators conducted a study to learn more.
The investigators analyzed hTERT expression level in 176 cases of RCC, requiring that each tumor had three core biopsies because of concerns of heterogeneity. The population consisted of 113 clear cell, 12 type I papillary, 20 type II papillary, and 31 chromophobe subtypes. Patient and clinicopathologic features were compared with survival and hTERT expression. Median follow-up time was 42 months.
Correlations between hTERT expression and disease characteristics were pronounced in cases of ccRCC, compared with other subtypes. In ccRCC, hTERT expression was significantly associated with tumor stage, nucleolar grade, tumor size, microvascular invasion, lymph node invasion, renal pelvis involvement, renal sinus fat involvement, Gerota fascia invasion, and distant metastasis. Survival analysis showed that DSS of ccRCC patients with high hTERT expression was 58 months, compared with 68 months for those with low hTERT expression (P =.012). Other parameters associated with survival were nucleolar grade, tumor stage, and tumor size.
For type I and II papillary subtypes, associations were found between hTERT expression and tumor stage and distant metastasis. In contrast, chromophobe RCC revealed no such relationships. No associations were found between hTERT expression and survival in any of these three latter subtypes, for slightly different reasons; no patients with type I disease died of renal cancer, disallowing creation of a Kaplan-Meier survival curve, whereas type II and chromophobe survival curves revealed insignificant relationships with hTERT expression. Along the same lines, no clinicopathologic characteristics of these subtypes were tied with survival.
“From these findings we are able to conclude that hTERT protein expression may be a novel prognostic indicator of worse outcome in tumor biopsies of patients with ccRCC, if follow up time is more prolonged,” the authors wrote. They noted that “telomerase is an attractive and ideal target for therapy due to overexpression in the majority of malignancies and low or nonexpression in most somatic cells.”
The study was funded by the Iran National Science Foundation. The authors declared no conflicts of interest.
SOURCE: Zanjani LS et al. Pathology. 2018 Nov 19. doi: 10.1016/j.pathol.2018.08.019.
FROM PATHOLOGY
Key clinical point: Human telomerase reverse transcriptase (hTERT) protein expression is associated with clear cell renal carcinoma (ccRCC) tumor aggressiveness and disease-specific survival (DSS).
Major finding: DSS of ccRCC patients with high hTERT expression was 58 months, compared with 68 months for those with low hTERT expression (P equal to .012).
Study details: An analysis of hTERT protein expression and disease characteristics in 176 patients with RCC. The subtype population consisted of 113 clear cell, 12 type I papillary, 20 type II papillary, and 31 chromophobe cases.
Disclosures: The study was funded by the Iran National Science Foundation. The authors declared no conflicts of interest.
Source: Zanjani LS et al. Pathology. 2018 Nov 19. doi: 10.1016/j.pathol.2018.08.019.
Age-related gene expression may affect responses to RCC therapy
Older patients with ccRCC may respond better than younger patients to phosphoinositide 3-kinase (PI3K) or checkpoint inhibition because of age-related changes in gene expression, according to investigators.
This possibility was raised by in silico results from a broader study of gene expression patterns in clear cell renal carcinoma (ccRCC) and normal kidney tissues, reported lead author, Lara Feulner, MD, of the department of human genetics at McGill University and Genome Quebec Innovation Centre in Montreal.
“Several factors could contribute to the interindividual diversity among cancer patients,” the investigators wrote in a report published in Urologic Oncology.
“Their disease course could be affected not only by cell-intrinsic factors, but also by age-related changes impacting the vasculature, immune system and stroma. Little is known in this regard about ccRCC, a disease which affects adults across a wide age spectrum. Whether and how aging and comorbidities such as atherosclerosis may affect the biology and therapy of ccRCC has scarcely been considered,” they wrote.
The investigators explored this territory by analyzing datasets from The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) program of the International Cancer Genome Consortium. Using regression, pathway enrichment, and connectivity mapping analyses, they were able to determine associations between age and gene expression, cellular processes, and drug treatment responses, respectively.
The investigators reported that age-related gene expression patterns occurred commonly in both normal and tumor tissues. Associations were reproducible between TCGA and CAGEKID datasets for both classes of tissue (tumor samples, R equal to 0.416, P less than 2.2 x 10-16; normal samples, R equal to 0.403, P less than 2.2 x 10-16). Out of the top 1,000 age-associated genes in tumor samples from each dataset, 383 were commonly downregulated with age and 294 were commonly upregulated with age in both datasets (P less than 2.2 x 10-16).
Among cellular pathways, the investigators found opposite age-relationship patterns. For example, normal tissues upregulated extracellular matrix and cell adhesion pathways with age, whereas tumor tissues downregulated the same pathways. Similar patterns of opposition were found in metabolism and oxidation pathways. Other age-related patterns were noted in some immune pathways, such as upregulation of toll-like receptor and tumor necrosis factor 2 noncanonical NF-kappa-B signaling in tumors, which became more common with age. A closer look showed that upregulation of tumor necrosis factor signaling was more common in female patients, who also downregulated Notch pathways more often than men.
Analysis of treatment responses showed possible relationships with age-dependent gene expression and immunotherapy. Specifically, of 532 genes tied to programmed cell death protein 1 (PD-1) resistance, 69 were among the 383 genes downregulated in older patients with ccRCC (P less than 2.2 x 10-16; 4.05 fold-enrichment), suggesting that older patients may respond better to anti-PD-1 therapy than younger patients. Similarly, connectivity map analysis showed that age-dependent gene expression may improve candidacy of older ccRCC patients for PI3K inhibition.
“We now have evidence that there are notable differences in tumor-associated pathway regulation between younger and older ccRCC patients, which may be therapeutically actionable,” the authors concluded.
The study was funded by the Cancer Research Society operation grant, a Canadian Cancer Society Research Institute Innovation-to-Impact grant, and a Canadian Institutes of Health Research Foundation grant. The authors reported no conflicts of interest.
SOURCE: Feulner et al. Urol Onc. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.11.006.
Older patients with ccRCC may respond better than younger patients to phosphoinositide 3-kinase (PI3K) or checkpoint inhibition because of age-related changes in gene expression, according to investigators.
This possibility was raised by in silico results from a broader study of gene expression patterns in clear cell renal carcinoma (ccRCC) and normal kidney tissues, reported lead author, Lara Feulner, MD, of the department of human genetics at McGill University and Genome Quebec Innovation Centre in Montreal.
“Several factors could contribute to the interindividual diversity among cancer patients,” the investigators wrote in a report published in Urologic Oncology.
“Their disease course could be affected not only by cell-intrinsic factors, but also by age-related changes impacting the vasculature, immune system and stroma. Little is known in this regard about ccRCC, a disease which affects adults across a wide age spectrum. Whether and how aging and comorbidities such as atherosclerosis may affect the biology and therapy of ccRCC has scarcely been considered,” they wrote.
The investigators explored this territory by analyzing datasets from The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) program of the International Cancer Genome Consortium. Using regression, pathway enrichment, and connectivity mapping analyses, they were able to determine associations between age and gene expression, cellular processes, and drug treatment responses, respectively.
The investigators reported that age-related gene expression patterns occurred commonly in both normal and tumor tissues. Associations were reproducible between TCGA and CAGEKID datasets for both classes of tissue (tumor samples, R equal to 0.416, P less than 2.2 x 10-16; normal samples, R equal to 0.403, P less than 2.2 x 10-16). Out of the top 1,000 age-associated genes in tumor samples from each dataset, 383 were commonly downregulated with age and 294 were commonly upregulated with age in both datasets (P less than 2.2 x 10-16).
Among cellular pathways, the investigators found opposite age-relationship patterns. For example, normal tissues upregulated extracellular matrix and cell adhesion pathways with age, whereas tumor tissues downregulated the same pathways. Similar patterns of opposition were found in metabolism and oxidation pathways. Other age-related patterns were noted in some immune pathways, such as upregulation of toll-like receptor and tumor necrosis factor 2 noncanonical NF-kappa-B signaling in tumors, which became more common with age. A closer look showed that upregulation of tumor necrosis factor signaling was more common in female patients, who also downregulated Notch pathways more often than men.
Analysis of treatment responses showed possible relationships with age-dependent gene expression and immunotherapy. Specifically, of 532 genes tied to programmed cell death protein 1 (PD-1) resistance, 69 were among the 383 genes downregulated in older patients with ccRCC (P less than 2.2 x 10-16; 4.05 fold-enrichment), suggesting that older patients may respond better to anti-PD-1 therapy than younger patients. Similarly, connectivity map analysis showed that age-dependent gene expression may improve candidacy of older ccRCC patients for PI3K inhibition.
“We now have evidence that there are notable differences in tumor-associated pathway regulation between younger and older ccRCC patients, which may be therapeutically actionable,” the authors concluded.
The study was funded by the Cancer Research Society operation grant, a Canadian Cancer Society Research Institute Innovation-to-Impact grant, and a Canadian Institutes of Health Research Foundation grant. The authors reported no conflicts of interest.
SOURCE: Feulner et al. Urol Onc. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.11.006.
Older patients with ccRCC may respond better than younger patients to phosphoinositide 3-kinase (PI3K) or checkpoint inhibition because of age-related changes in gene expression, according to investigators.
This possibility was raised by in silico results from a broader study of gene expression patterns in clear cell renal carcinoma (ccRCC) and normal kidney tissues, reported lead author, Lara Feulner, MD, of the department of human genetics at McGill University and Genome Quebec Innovation Centre in Montreal.
“Several factors could contribute to the interindividual diversity among cancer patients,” the investigators wrote in a report published in Urologic Oncology.
“Their disease course could be affected not only by cell-intrinsic factors, but also by age-related changes impacting the vasculature, immune system and stroma. Little is known in this regard about ccRCC, a disease which affects adults across a wide age spectrum. Whether and how aging and comorbidities such as atherosclerosis may affect the biology and therapy of ccRCC has scarcely been considered,” they wrote.
The investigators explored this territory by analyzing datasets from The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) program of the International Cancer Genome Consortium. Using regression, pathway enrichment, and connectivity mapping analyses, they were able to determine associations between age and gene expression, cellular processes, and drug treatment responses, respectively.
The investigators reported that age-related gene expression patterns occurred commonly in both normal and tumor tissues. Associations were reproducible between TCGA and CAGEKID datasets for both classes of tissue (tumor samples, R equal to 0.416, P less than 2.2 x 10-16; normal samples, R equal to 0.403, P less than 2.2 x 10-16). Out of the top 1,000 age-associated genes in tumor samples from each dataset, 383 were commonly downregulated with age and 294 were commonly upregulated with age in both datasets (P less than 2.2 x 10-16).
Among cellular pathways, the investigators found opposite age-relationship patterns. For example, normal tissues upregulated extracellular matrix and cell adhesion pathways with age, whereas tumor tissues downregulated the same pathways. Similar patterns of opposition were found in metabolism and oxidation pathways. Other age-related patterns were noted in some immune pathways, such as upregulation of toll-like receptor and tumor necrosis factor 2 noncanonical NF-kappa-B signaling in tumors, which became more common with age. A closer look showed that upregulation of tumor necrosis factor signaling was more common in female patients, who also downregulated Notch pathways more often than men.
Analysis of treatment responses showed possible relationships with age-dependent gene expression and immunotherapy. Specifically, of 532 genes tied to programmed cell death protein 1 (PD-1) resistance, 69 were among the 383 genes downregulated in older patients with ccRCC (P less than 2.2 x 10-16; 4.05 fold-enrichment), suggesting that older patients may respond better to anti-PD-1 therapy than younger patients. Similarly, connectivity map analysis showed that age-dependent gene expression may improve candidacy of older ccRCC patients for PI3K inhibition.
“We now have evidence that there are notable differences in tumor-associated pathway regulation between younger and older ccRCC patients, which may be therapeutically actionable,” the authors concluded.
The study was funded by the Cancer Research Society operation grant, a Canadian Cancer Society Research Institute Innovation-to-Impact grant, and a Canadian Institutes of Health Research Foundation grant. The authors reported no conflicts of interest.
SOURCE: Feulner et al. Urol Onc. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.11.006.
FROM UROLOGIC ONCOLOGY
Key clinical point: Older patients with ccRCC may respond better than younger patients to phosphoinositide 3-kinase or checkpoint inhibition due to age-related changes in gene expression.
Major finding: Out of the top 1,000 age-associated genes in tumor samples, 383 were commonly downregulated with age and 294 were commonly upregulated with age in two large data sets (P less than 2.2 x 10-16).
Study details: An analysis of data from The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) program of the International Cancer Genome Consortium.
Disclosures: The study was funded by the Cancer Research Society operation grant, a Canadian Cancer Society Research Institute Innovation-to-Impact grant, and a Canadian Institutes of Health Research Foundation grant.
Source: Feulner et al. Urol Oncol. 2018 Nov 23. doi: 10.1016/j.urolonc.2018.11.006.
Elderly NHL patients have higher NRM after HSCT
A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).
The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.
However, the 3-year rate of relapse was similar across the age groups.
Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.
The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.
The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).
At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.
Results
The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).
NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).
Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).
In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).
The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.
After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”
Therefore, age remains an independent risk factor.
The investigators did not report conflicts of interest.
A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).
The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.
However, the 3-year rate of relapse was similar across the age groups.
Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.
The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.
The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).
At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.
Results
The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).
NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).
Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).
In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).
The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.
After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”
Therefore, age remains an independent risk factor.
The investigators did not report conflicts of interest.
A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).
The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.
However, the 3-year rate of relapse was similar across the age groups.
Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.
The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.
The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).
At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.
Results
The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).
NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).
Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).
In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).
The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.
After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”
Therefore, age remains an independent risk factor.
The investigators did not report conflicts of interest.
DECLARE: Dapagliflozin improves some cardiovascular, renal outcomes
For patients with type 2 diabetes who have or are at risk for atherosclerotic cardiovascular disease, do, according to investigators.
A composite measure of major adverse cardiovascular events (MACE), including cardiovascular death, ischemic stroke, or myocardial infarction, was comparable between dapagliflozin and placebo; in contrast, diabetic ketoacidosis occurred more frequently with dapagliflozin, reported lead author Stephen D. Wiviott, MD at the American Heart Association scientific sessions.
“As a result of [the] intersection of diabetes, atherosclerotic cardiovascular disease, and heart failure, the importance of determining diabetes therapies that are not only safe but also effective in reducing cardiovascular risk is paramount,” Dr. Wiviott and colleagues wrote in an article published simultaneously in the New England Journal of Medicine.
“Dapagliflozin is a selective inhibitor of sodium–glucose cotransporter (SGLT2) that blocks glucose resorption in the proximal tubule of the kidney and promotes glucosuria,” the investigators wrote. “Other SGLT2 inhibitors have shown favorable cardiovascular effects, including a reduction in the risk of hospitalization for heart failure, predominantly in patients with type 2 diabetes and established cardiovascular disease; they have also been shown to delay the progression of kidney disease.”
The goal of the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 (DECLARE–TIMI 58) trial was to determine what impact, if any, dapagliflozin has on renal and cardiovascular outcomes in a diverse array of patients with or at risk for atherosclerotic cardiovascular disease. The phase III, double-blind, placebo-controlled, randomized study involved 17,160 adults with type 2 diabetes from 33 countries. Of these, nearly 7,000 patients had atherosclerotic cardiovascular disease and the remaining 10,000 or so patients had multiple risk factors for atherosclerotic cardiovascular disease. Patients were at least 40 years of age, had a creatinine clearance of at least 60 mL/minute, and a HbA1c level between 6.5% and 12.0%. They were randomly assigned to receive either dapagliflozin 10 mg daily or placebo. Every 6 months, patients had laboratory testing with in-person follow-up for safety, clinical response, and adherence; patients were contacted via telephone at the halfway point between appointments (3 months).
The primary safety outcome of the study was major adverse cardiovascular outcomes (MACE: ischemic stroke, myocardial infarction, or cardiovascular death). The trial began with MACE as the sole primary safety outcome, as guided by the Food and Drug Administration, but this changed before completion. “During the trial,” the investigators explained, “compelling external scientific information from the EMPA-REG OUTCOME trial, which evaluated another SGLT2 inhibitor, showed greater benefit with respect to cardiovascular death and hospitalization for heart failure than with respect to MACE.” Therefore, before data were known, the investigators added a second primary outcome: a composite of cardiovascular death or hospitalization for heart failure. The two secondary outcomes were a renal composite (new end-stage renal disease, estimated glomerular filtration rate decrease by at least 40% to less than 60 m/min per 1.73 m2 of body-surface area, or death from renal or cardiovascular disease), and death from any cause.
The primary safety outcome (MACE rate) showed that dapagliflozin was noninferior to placebo (upper boundary of the 95% confidence interval, less than 1.3; P less than .001 for noninferiority). Although the MACE rate was similar between treatment groups (8.8% for dapagliflozin vs 9.4% for placebo; P = .017), the composite rate of cardiovascular death or hospitalization for heart failure was 17% lower for patients receiving dapagliflozin, compared with those who received placebo (4.9% vs 5.8%); this latter finding was attributable mostly to a 27% lower risk of hospitalization, instead of the 2% reduction in cardiovascular death. Seven percent fewer deaths of any kind were observed in the dapagliflozin group (6.2%) than in the placebo group (6.6%). Renal events saw a bigger difference, of 23% (4.3% vs 5.6%).
Statistically significant adverse events seen in more dapagliflozin than placebo patients included diabetic ketoacidosis and genital infection. Dr. Wiviott noted that adverse events favoring hypoglycemia included major hypoglycemia and bladder cancer..
“We did not find that SGLT2 inhibition with dapagliflozin resulted in a lower rate of cardiovascular death or death from any cause than placebo, a finding that contrasts with that in the EMPA-REG OUTCOME trial,” the investigators noted. Apart from possible differences in drugs within the same class, the investigators pointed to more restrictive renal criteria in the DECLARE trial and possible inherent differences between patient populations, among other possible factors.
“…in a broad population of patients with type 2 diabetes [dapagliflozin] did result in a significantly lower rate of cardiovascular death or hospitalization for heart failure than placebo, with additional findings supporting a possible lower rate of adverse renal outcomes,” the investigators concluded.
The DECLARE-TIMI 58 trial was sponsored by AstraZeneca and Bristol-Myers Squibb. Authors reported various financial affiliations with Eisai, Medtronic, Sanofi Aventis, Abbott, Regeneron, and others.
SOURCE: Wiviott et al. N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1812389
For patients with type 2 diabetes who have or are at risk for atherosclerotic cardiovascular disease, do, according to investigators.
A composite measure of major adverse cardiovascular events (MACE), including cardiovascular death, ischemic stroke, or myocardial infarction, was comparable between dapagliflozin and placebo; in contrast, diabetic ketoacidosis occurred more frequently with dapagliflozin, reported lead author Stephen D. Wiviott, MD at the American Heart Association scientific sessions.
“As a result of [the] intersection of diabetes, atherosclerotic cardiovascular disease, and heart failure, the importance of determining diabetes therapies that are not only safe but also effective in reducing cardiovascular risk is paramount,” Dr. Wiviott and colleagues wrote in an article published simultaneously in the New England Journal of Medicine.
“Dapagliflozin is a selective inhibitor of sodium–glucose cotransporter (SGLT2) that blocks glucose resorption in the proximal tubule of the kidney and promotes glucosuria,” the investigators wrote. “Other SGLT2 inhibitors have shown favorable cardiovascular effects, including a reduction in the risk of hospitalization for heart failure, predominantly in patients with type 2 diabetes and established cardiovascular disease; they have also been shown to delay the progression of kidney disease.”
The goal of the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 (DECLARE–TIMI 58) trial was to determine what impact, if any, dapagliflozin has on renal and cardiovascular outcomes in a diverse array of patients with or at risk for atherosclerotic cardiovascular disease. The phase III, double-blind, placebo-controlled, randomized study involved 17,160 adults with type 2 diabetes from 33 countries. Of these, nearly 7,000 patients had atherosclerotic cardiovascular disease and the remaining 10,000 or so patients had multiple risk factors for atherosclerotic cardiovascular disease. Patients were at least 40 years of age, had a creatinine clearance of at least 60 mL/minute, and a HbA1c level between 6.5% and 12.0%. They were randomly assigned to receive either dapagliflozin 10 mg daily or placebo. Every 6 months, patients had laboratory testing with in-person follow-up for safety, clinical response, and adherence; patients were contacted via telephone at the halfway point between appointments (3 months).
The primary safety outcome of the study was major adverse cardiovascular outcomes (MACE: ischemic stroke, myocardial infarction, or cardiovascular death). The trial began with MACE as the sole primary safety outcome, as guided by the Food and Drug Administration, but this changed before completion. “During the trial,” the investigators explained, “compelling external scientific information from the EMPA-REG OUTCOME trial, which evaluated another SGLT2 inhibitor, showed greater benefit with respect to cardiovascular death and hospitalization for heart failure than with respect to MACE.” Therefore, before data were known, the investigators added a second primary outcome: a composite of cardiovascular death or hospitalization for heart failure. The two secondary outcomes were a renal composite (new end-stage renal disease, estimated glomerular filtration rate decrease by at least 40% to less than 60 m/min per 1.73 m2 of body-surface area, or death from renal or cardiovascular disease), and death from any cause.
The primary safety outcome (MACE rate) showed that dapagliflozin was noninferior to placebo (upper boundary of the 95% confidence interval, less than 1.3; P less than .001 for noninferiority). Although the MACE rate was similar between treatment groups (8.8% for dapagliflozin vs 9.4% for placebo; P = .017), the composite rate of cardiovascular death or hospitalization for heart failure was 17% lower for patients receiving dapagliflozin, compared with those who received placebo (4.9% vs 5.8%); this latter finding was attributable mostly to a 27% lower risk of hospitalization, instead of the 2% reduction in cardiovascular death. Seven percent fewer deaths of any kind were observed in the dapagliflozin group (6.2%) than in the placebo group (6.6%). Renal events saw a bigger difference, of 23% (4.3% vs 5.6%).
Statistically significant adverse events seen in more dapagliflozin than placebo patients included diabetic ketoacidosis and genital infection. Dr. Wiviott noted that adverse events favoring hypoglycemia included major hypoglycemia and bladder cancer..
“We did not find that SGLT2 inhibition with dapagliflozin resulted in a lower rate of cardiovascular death or death from any cause than placebo, a finding that contrasts with that in the EMPA-REG OUTCOME trial,” the investigators noted. Apart from possible differences in drugs within the same class, the investigators pointed to more restrictive renal criteria in the DECLARE trial and possible inherent differences between patient populations, among other possible factors.
“…in a broad population of patients with type 2 diabetes [dapagliflozin] did result in a significantly lower rate of cardiovascular death or hospitalization for heart failure than placebo, with additional findings supporting a possible lower rate of adverse renal outcomes,” the investigators concluded.
The DECLARE-TIMI 58 trial was sponsored by AstraZeneca and Bristol-Myers Squibb. Authors reported various financial affiliations with Eisai, Medtronic, Sanofi Aventis, Abbott, Regeneron, and others.
SOURCE: Wiviott et al. N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1812389
For patients with type 2 diabetes who have or are at risk for atherosclerotic cardiovascular disease, do, according to investigators.
A composite measure of major adverse cardiovascular events (MACE), including cardiovascular death, ischemic stroke, or myocardial infarction, was comparable between dapagliflozin and placebo; in contrast, diabetic ketoacidosis occurred more frequently with dapagliflozin, reported lead author Stephen D. Wiviott, MD at the American Heart Association scientific sessions.
“As a result of [the] intersection of diabetes, atherosclerotic cardiovascular disease, and heart failure, the importance of determining diabetes therapies that are not only safe but also effective in reducing cardiovascular risk is paramount,” Dr. Wiviott and colleagues wrote in an article published simultaneously in the New England Journal of Medicine.
“Dapagliflozin is a selective inhibitor of sodium–glucose cotransporter (SGLT2) that blocks glucose resorption in the proximal tubule of the kidney and promotes glucosuria,” the investigators wrote. “Other SGLT2 inhibitors have shown favorable cardiovascular effects, including a reduction in the risk of hospitalization for heart failure, predominantly in patients with type 2 diabetes and established cardiovascular disease; they have also been shown to delay the progression of kidney disease.”
The goal of the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 (DECLARE–TIMI 58) trial was to determine what impact, if any, dapagliflozin has on renal and cardiovascular outcomes in a diverse array of patients with or at risk for atherosclerotic cardiovascular disease. The phase III, double-blind, placebo-controlled, randomized study involved 17,160 adults with type 2 diabetes from 33 countries. Of these, nearly 7,000 patients had atherosclerotic cardiovascular disease and the remaining 10,000 or so patients had multiple risk factors for atherosclerotic cardiovascular disease. Patients were at least 40 years of age, had a creatinine clearance of at least 60 mL/minute, and a HbA1c level between 6.5% and 12.0%. They were randomly assigned to receive either dapagliflozin 10 mg daily or placebo. Every 6 months, patients had laboratory testing with in-person follow-up for safety, clinical response, and adherence; patients were contacted via telephone at the halfway point between appointments (3 months).
The primary safety outcome of the study was major adverse cardiovascular outcomes (MACE: ischemic stroke, myocardial infarction, or cardiovascular death). The trial began with MACE as the sole primary safety outcome, as guided by the Food and Drug Administration, but this changed before completion. “During the trial,” the investigators explained, “compelling external scientific information from the EMPA-REG OUTCOME trial, which evaluated another SGLT2 inhibitor, showed greater benefit with respect to cardiovascular death and hospitalization for heart failure than with respect to MACE.” Therefore, before data were known, the investigators added a second primary outcome: a composite of cardiovascular death or hospitalization for heart failure. The two secondary outcomes were a renal composite (new end-stage renal disease, estimated glomerular filtration rate decrease by at least 40% to less than 60 m/min per 1.73 m2 of body-surface area, or death from renal or cardiovascular disease), and death from any cause.
The primary safety outcome (MACE rate) showed that dapagliflozin was noninferior to placebo (upper boundary of the 95% confidence interval, less than 1.3; P less than .001 for noninferiority). Although the MACE rate was similar between treatment groups (8.8% for dapagliflozin vs 9.4% for placebo; P = .017), the composite rate of cardiovascular death or hospitalization for heart failure was 17% lower for patients receiving dapagliflozin, compared with those who received placebo (4.9% vs 5.8%); this latter finding was attributable mostly to a 27% lower risk of hospitalization, instead of the 2% reduction in cardiovascular death. Seven percent fewer deaths of any kind were observed in the dapagliflozin group (6.2%) than in the placebo group (6.6%). Renal events saw a bigger difference, of 23% (4.3% vs 5.6%).
Statistically significant adverse events seen in more dapagliflozin than placebo patients included diabetic ketoacidosis and genital infection. Dr. Wiviott noted that adverse events favoring hypoglycemia included major hypoglycemia and bladder cancer..
“We did not find that SGLT2 inhibition with dapagliflozin resulted in a lower rate of cardiovascular death or death from any cause than placebo, a finding that contrasts with that in the EMPA-REG OUTCOME trial,” the investigators noted. Apart from possible differences in drugs within the same class, the investigators pointed to more restrictive renal criteria in the DECLARE trial and possible inherent differences between patient populations, among other possible factors.
“…in a broad population of patients with type 2 diabetes [dapagliflozin] did result in a significantly lower rate of cardiovascular death or hospitalization for heart failure than placebo, with additional findings supporting a possible lower rate of adverse renal outcomes,” the investigators concluded.
The DECLARE-TIMI 58 trial was sponsored by AstraZeneca and Bristol-Myers Squibb. Authors reported various financial affiliations with Eisai, Medtronic, Sanofi Aventis, Abbott, Regeneron, and others.
SOURCE: Wiviott et al. N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1812389
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: For patients with type 2 diabetes who have or are at risk for atherosclerotic cardiovascular disease, dapagliflozin is associated with a lower composite rate of cardiovascular death or hospitalization for heart failure, compared with placebo.
Major finding: Of patients taking dapagliflozin, 4.9% died of cardiovascular disease or were hospitalized for heart failure, compared with 5.8% of patients receiving placebo (P = .005).
Study details: The phase III DECLARE–TIMI 58 trial was a double-blind, placebo-controlled, randomized study that involved 17,160 patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease.
Disclosures: DECLARE–TIMI 58 was sponsored by AstraZeneca and Bristol-Myers Squibb. Authors reported various financial affiliations with Eisai, Medtronic, Sanofi Aventis, Abbott, Regeneron, and others.
Source: Wiviott et al. N Engl J Med. 2018 Nov 10. doi: ___________
SRS beats surgery in early control of brain mets, advantage fades with time
Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.
By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.
“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.
The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.
Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).
After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.
“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.
The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.
SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.
By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.
“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.
The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.
Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).
After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.
“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.
The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.
SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.
By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.
“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.
The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.
Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).
After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.
“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.
The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.
SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
FROM JAMA ONCOLOGY
Key clinical point: Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than surgical resection, but this advantage fades with time.
Major finding: Patients treated with surgery were more likely to have local recurrence in the first 3 months following treatment, compared with patients treated with SRS (hazard ratio, 5.94).
Study details: An exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial. Analysis involved 268 patients with one to three brain metastases who underwent whole-brain radiotherapy or observation after SRS (n = 154) or complete surgical resection (n = 114).
Disclosures: The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. Dr. Handorf reported financial compensation from Pfizer, via her institution.
Source: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
Cardiovascular disease risk unchanged in men with hemophilia A
Concerns may be unfounded for risks of earlier-onset cardiovascular disease in men with hemophilia A, according to investigators.
Cardiovascular comorbidities between groups were generally comparable, regardless of hemophilia A status, reported lead author Thomas J. Humphries, MD, of Bayer, and his colleagues.
“To date, there have been conflicting data in the literature regarding the risks of [cardiovascular] comorbidities in patients with hemophilia A, compared with the general population,” the investigators wrote in Advances in Medical Sciences. “Some studies have reported lower mortality from [cardiovascular] diseases and/or decreased atherogenesis in patients with hemophilia … conversely, other reports indicate comparable or higher [cardiovascular] comorbidities in patients with hemophilia, compared with the general population.”
In two previous commercial database reviews conducted by Dr. Humphries and his colleagues, cardiovascular disease appeared to occur more commonly and at a younger age in men with hemophilia A. More concerning, patients aged under 40 years showed elevated incidence of stroke and thrombosis. The authors sought to clarify these findings in the present study.
The retrospective chart review involved 74 men with hemophilia A and 222 men without the condition, matched by study year, payer type, race, and age. Patients presented at any of 31 medical facilities within the Henry Ford Health System in Detroit. Diagnoses were made between Jan. 1, 1995, and Dec. 31, 2014.
For the most part there were no significant differences in cardiovascular disease prevalence between the two cohorts. Rates of hypertension, obesity, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease were numerically higher in the control group, but those differences were not statistically significant. There were significantly higher prevalence rates for diabetes (P = .0108) and hyperlipidemia (P = .0001) in the control group versus patients with hemophilia A.
The investigators pointed out that meaningful statistical differences using standardized differences were not reached for venous and arterial thrombosis and atrial fibrillation.
“It is worth noting that in the hemophilia A group, hypertension appeared first in the 18- to 29-year age group, as did venous thrombosis,” the investigators wrote, suggesting that monitoring, starting in the late teens, may be warranted.
The investigators also noted multiple study limitations, notably the small sample size, compared with commercial databases that were reviewed in previous studies. Additionally, the severity of disease was unknown for some of the hemophilia A patients and the study only followed patients for 1 year.
“The results of this retrospective chart review did not confirm diffuse statistically significant differences in [cardiovascular] comorbidities and their earlier onset in hemophilia A versus controls,” the investigators concluded.
The study was funded by Bayer. Three of the authors were employed by Bayer when the study was conducted. Other authors reported employment with Xcenda and the Henry Ford Health System and research funding from Xcenda.
SOURCE: Humphries TJ et al. Adv Med Sci. 2018;63(2):329-33.
Concerns may be unfounded for risks of earlier-onset cardiovascular disease in men with hemophilia A, according to investigators.
Cardiovascular comorbidities between groups were generally comparable, regardless of hemophilia A status, reported lead author Thomas J. Humphries, MD, of Bayer, and his colleagues.
“To date, there have been conflicting data in the literature regarding the risks of [cardiovascular] comorbidities in patients with hemophilia A, compared with the general population,” the investigators wrote in Advances in Medical Sciences. “Some studies have reported lower mortality from [cardiovascular] diseases and/or decreased atherogenesis in patients with hemophilia … conversely, other reports indicate comparable or higher [cardiovascular] comorbidities in patients with hemophilia, compared with the general population.”
In two previous commercial database reviews conducted by Dr. Humphries and his colleagues, cardiovascular disease appeared to occur more commonly and at a younger age in men with hemophilia A. More concerning, patients aged under 40 years showed elevated incidence of stroke and thrombosis. The authors sought to clarify these findings in the present study.
The retrospective chart review involved 74 men with hemophilia A and 222 men without the condition, matched by study year, payer type, race, and age. Patients presented at any of 31 medical facilities within the Henry Ford Health System in Detroit. Diagnoses were made between Jan. 1, 1995, and Dec. 31, 2014.
For the most part there were no significant differences in cardiovascular disease prevalence between the two cohorts. Rates of hypertension, obesity, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease were numerically higher in the control group, but those differences were not statistically significant. There were significantly higher prevalence rates for diabetes (P = .0108) and hyperlipidemia (P = .0001) in the control group versus patients with hemophilia A.
The investigators pointed out that meaningful statistical differences using standardized differences were not reached for venous and arterial thrombosis and atrial fibrillation.
“It is worth noting that in the hemophilia A group, hypertension appeared first in the 18- to 29-year age group, as did venous thrombosis,” the investigators wrote, suggesting that monitoring, starting in the late teens, may be warranted.
The investigators also noted multiple study limitations, notably the small sample size, compared with commercial databases that were reviewed in previous studies. Additionally, the severity of disease was unknown for some of the hemophilia A patients and the study only followed patients for 1 year.
“The results of this retrospective chart review did not confirm diffuse statistically significant differences in [cardiovascular] comorbidities and their earlier onset in hemophilia A versus controls,” the investigators concluded.
The study was funded by Bayer. Three of the authors were employed by Bayer when the study was conducted. Other authors reported employment with Xcenda and the Henry Ford Health System and research funding from Xcenda.
SOURCE: Humphries TJ et al. Adv Med Sci. 2018;63(2):329-33.
Concerns may be unfounded for risks of earlier-onset cardiovascular disease in men with hemophilia A, according to investigators.
Cardiovascular comorbidities between groups were generally comparable, regardless of hemophilia A status, reported lead author Thomas J. Humphries, MD, of Bayer, and his colleagues.
“To date, there have been conflicting data in the literature regarding the risks of [cardiovascular] comorbidities in patients with hemophilia A, compared with the general population,” the investigators wrote in Advances in Medical Sciences. “Some studies have reported lower mortality from [cardiovascular] diseases and/or decreased atherogenesis in patients with hemophilia … conversely, other reports indicate comparable or higher [cardiovascular] comorbidities in patients with hemophilia, compared with the general population.”
In two previous commercial database reviews conducted by Dr. Humphries and his colleagues, cardiovascular disease appeared to occur more commonly and at a younger age in men with hemophilia A. More concerning, patients aged under 40 years showed elevated incidence of stroke and thrombosis. The authors sought to clarify these findings in the present study.
The retrospective chart review involved 74 men with hemophilia A and 222 men without the condition, matched by study year, payer type, race, and age. Patients presented at any of 31 medical facilities within the Henry Ford Health System in Detroit. Diagnoses were made between Jan. 1, 1995, and Dec. 31, 2014.
For the most part there were no significant differences in cardiovascular disease prevalence between the two cohorts. Rates of hypertension, obesity, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease were numerically higher in the control group, but those differences were not statistically significant. There were significantly higher prevalence rates for diabetes (P = .0108) and hyperlipidemia (P = .0001) in the control group versus patients with hemophilia A.
The investigators pointed out that meaningful statistical differences using standardized differences were not reached for venous and arterial thrombosis and atrial fibrillation.
“It is worth noting that in the hemophilia A group, hypertension appeared first in the 18- to 29-year age group, as did venous thrombosis,” the investigators wrote, suggesting that monitoring, starting in the late teens, may be warranted.
The investigators also noted multiple study limitations, notably the small sample size, compared with commercial databases that were reviewed in previous studies. Additionally, the severity of disease was unknown for some of the hemophilia A patients and the study only followed patients for 1 year.
“The results of this retrospective chart review did not confirm diffuse statistically significant differences in [cardiovascular] comorbidities and their earlier onset in hemophilia A versus controls,” the investigators concluded.
The study was funded by Bayer. Three of the authors were employed by Bayer when the study was conducted. Other authors reported employment with Xcenda and the Henry Ford Health System and research funding from Xcenda.
SOURCE: Humphries TJ et al. Adv Med Sci. 2018;63(2):329-33.
FROM ADVANCES IN MEDICAL SCIENCES
Key clinical point:
Major finding: Prevalence rates of diabetes (P = .0108) and hyperlipidemia (P = .0001) were higher in the control group, compared with patients with hemophilia A.
Study details: A retrospective chart review involving 74 men with hemophilia A and 222 men without the condition, matched by study year, payer type, race, and age.
Disclosures: The study was funded by Bayer. Three authors were employed by Bayer when the study was conducted. Other authors reported employment by Xcenda and the Henry Ford Health System and research funding from Xcenda.
Source: Humphries TJ et al. Adv Med Sci. 2018;63(2):329-33.
Checkpoint inhibitor doubles 3-year survival rate of BRAF wild-type advanced melanoma
For previously untreated patients with BRAF wild-type advanced melanoma, the antiprogrammed death-ligand 1 agent nivolumab dramatically improved overall survival (OS), compared with standard first-line chemotherapy, according to new data from the CheckMate 066 trial.
At the 3-year follow-up, more than twice as many nivolumab-treated patients were alive, compared with those who received dacarbazine, reported lead author Paolo A. Ascierto, MD, director of the unit of melanoma, cancer immunotherapy, and innovative therapy at the Istituto Nazionale Tumori Fondazione Pascale in Naples, Italy, and his colleagues. Longer median progression-free survival (PFS) and higher complete response rates were also reported.
“The results of this 3-year follow-up analysis provided evidence for a durable survival benefit with nivolumab monotherapy in patients with previously untreated BRAF wild-type advanced melanoma,” the investigators wrote in JAMA Oncology.
The double-blind, phase 3 trial involved 418 patients with unresectable, previously untreated stage III or IV melanoma not exhibiting a BRAF mutation. Patients were randomized to receive either nivolumab (n = 210; 3 mg/kg every 2 weeks plus placebo every 3 weeks) or dacarbazine (n = 208; 1,000 mg/m2 every 3 weeks plus placebo every 2 weeks). Treatment continued until unacceptable toxicity or disease progression occurred.
The results showed dramatic benefits, measured by OS and PFS, when patients were treated with nivolumab. The 3-year OS rate was 51.2% in the nivolumab group, compared with 21.6% in the dacarbazine group, an approximate 130% difference. Median OS and median PFS were also multiplied by the checkpoint inhibitor, showing 230% and 130% improvements, respectively (OS, 37.5 months vs. 11.2 months; PFS, 5.1 months vs. 2.2 months; P less than .001). Grade 3 or higher treatment-related adverse events (AEs) were comparable between treatment arms (nivolumab, 15.0% vs. dacarbazine, 17.6%).
“Responses to nivolumab were long lasting in many patients who discontinued treatment, with most patients who stopped treatment still alive and without disease progression at the time of the last assessment,” the investigators wrote.
“Collectively, our results showed durable responses and long-term survival with nivolumab monotherapy, with no new AEs developing at late time points,” they concluded.
The study was funded by Bristol-Myers Squibb. The authors reported financial relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, Amgen, and others.
SOURCE: Ascierto PA et al. JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514.
For previously untreated patients with BRAF wild-type advanced melanoma, the antiprogrammed death-ligand 1 agent nivolumab dramatically improved overall survival (OS), compared with standard first-line chemotherapy, according to new data from the CheckMate 066 trial.
At the 3-year follow-up, more than twice as many nivolumab-treated patients were alive, compared with those who received dacarbazine, reported lead author Paolo A. Ascierto, MD, director of the unit of melanoma, cancer immunotherapy, and innovative therapy at the Istituto Nazionale Tumori Fondazione Pascale in Naples, Italy, and his colleagues. Longer median progression-free survival (PFS) and higher complete response rates were also reported.
“The results of this 3-year follow-up analysis provided evidence for a durable survival benefit with nivolumab monotherapy in patients with previously untreated BRAF wild-type advanced melanoma,” the investigators wrote in JAMA Oncology.
The double-blind, phase 3 trial involved 418 patients with unresectable, previously untreated stage III or IV melanoma not exhibiting a BRAF mutation. Patients were randomized to receive either nivolumab (n = 210; 3 mg/kg every 2 weeks plus placebo every 3 weeks) or dacarbazine (n = 208; 1,000 mg/m2 every 3 weeks plus placebo every 2 weeks). Treatment continued until unacceptable toxicity or disease progression occurred.
The results showed dramatic benefits, measured by OS and PFS, when patients were treated with nivolumab. The 3-year OS rate was 51.2% in the nivolumab group, compared with 21.6% in the dacarbazine group, an approximate 130% difference. Median OS and median PFS were also multiplied by the checkpoint inhibitor, showing 230% and 130% improvements, respectively (OS, 37.5 months vs. 11.2 months; PFS, 5.1 months vs. 2.2 months; P less than .001). Grade 3 or higher treatment-related adverse events (AEs) were comparable between treatment arms (nivolumab, 15.0% vs. dacarbazine, 17.6%).
“Responses to nivolumab were long lasting in many patients who discontinued treatment, with most patients who stopped treatment still alive and without disease progression at the time of the last assessment,” the investigators wrote.
“Collectively, our results showed durable responses and long-term survival with nivolumab monotherapy, with no new AEs developing at late time points,” they concluded.
The study was funded by Bristol-Myers Squibb. The authors reported financial relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, Amgen, and others.
SOURCE: Ascierto PA et al. JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514.
For previously untreated patients with BRAF wild-type advanced melanoma, the antiprogrammed death-ligand 1 agent nivolumab dramatically improved overall survival (OS), compared with standard first-line chemotherapy, according to new data from the CheckMate 066 trial.
At the 3-year follow-up, more than twice as many nivolumab-treated patients were alive, compared with those who received dacarbazine, reported lead author Paolo A. Ascierto, MD, director of the unit of melanoma, cancer immunotherapy, and innovative therapy at the Istituto Nazionale Tumori Fondazione Pascale in Naples, Italy, and his colleagues. Longer median progression-free survival (PFS) and higher complete response rates were also reported.
“The results of this 3-year follow-up analysis provided evidence for a durable survival benefit with nivolumab monotherapy in patients with previously untreated BRAF wild-type advanced melanoma,” the investigators wrote in JAMA Oncology.
The double-blind, phase 3 trial involved 418 patients with unresectable, previously untreated stage III or IV melanoma not exhibiting a BRAF mutation. Patients were randomized to receive either nivolumab (n = 210; 3 mg/kg every 2 weeks plus placebo every 3 weeks) or dacarbazine (n = 208; 1,000 mg/m2 every 3 weeks plus placebo every 2 weeks). Treatment continued until unacceptable toxicity or disease progression occurred.
The results showed dramatic benefits, measured by OS and PFS, when patients were treated with nivolumab. The 3-year OS rate was 51.2% in the nivolumab group, compared with 21.6% in the dacarbazine group, an approximate 130% difference. Median OS and median PFS were also multiplied by the checkpoint inhibitor, showing 230% and 130% improvements, respectively (OS, 37.5 months vs. 11.2 months; PFS, 5.1 months vs. 2.2 months; P less than .001). Grade 3 or higher treatment-related adverse events (AEs) were comparable between treatment arms (nivolumab, 15.0% vs. dacarbazine, 17.6%).
“Responses to nivolumab were long lasting in many patients who discontinued treatment, with most patients who stopped treatment still alive and without disease progression at the time of the last assessment,” the investigators wrote.
“Collectively, our results showed durable responses and long-term survival with nivolumab monotherapy, with no new AEs developing at late time points,” they concluded.
The study was funded by Bristol-Myers Squibb. The authors reported financial relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, Amgen, and others.
SOURCE: Ascierto PA et al. JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514.
FROM JAMA ONCOLOGY
Key clinical point: For previously untreated patients with BRAF wild-type advanced melanoma, the checkpoint inhibitor nivolumab dramatically improved overall survival, compared with standard first-line chemotherapy.
Major finding: The 3-year overall survival rate for patients treated with nivolumab was 51.2%, compared with 21.6% for those who received dacarbazine.
Study details: CheckMate 066 is an ongoing, phase 3, double-blind trial involving 418 patients with BRAF wild-type advanced melanoma.
Disclosures: The study was funded by Bristol-Myers Squibb. The authors reported financial relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, Amgen, and others.
Source: Ascierto PA et al. JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514.
Older age predicts mortality after alloHCT in NHL, but not relapse
Elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within 1 year of allogeneic hematopoietic cell transplantation (alloHCT), compared with younger or middle-age patients, according to investigators.
Comorbidities also increased risks of nonrelapse mortality (NRM) at 1 year, but to a lesser extent than that of elderly status, reported lead author Charalampia Kyriakou, MD, PhD, of the department of haematology at University College London Hospital and London North West University Healthcare NHS Trust, and her colleagues.
“Although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group,” the investigators wrote in Biology of Blood and Marrow Transplantation.
This decision is becoming more common, they noted. “With the advent of reduced-intensity conditioning (RIC) strategies and other improvements in transplantation technology, alloHCT is being increasingly considered in elderly patients with [relapsed and refractory] NHL.”
The retrospective study analyzed 3,919 patients with NHL who underwent alloHCT between 2003 and 2013. Patients were sorted into three age groups: young (18-50 years), middle age (51-65 years), or elderly (66-77 years).
Disease types also were reported: 1,461 patients had follicular lymphoma (FL; 37%), 1,192 had diffuse large B cell lymphoma (DLBCL; 30%), 823 had mantle cell lymphoma (MCL; 21%), and 443 had peripheral T cell lymphoma (PTCL; 11%).
At the time of alloHCT, about 85% of patients were chemosensitive, with the remainder being chemorefractory. The age groups had similar patient characteristics, with exceptions noted for unrelated donors, MCL, and RIC, which became increasingly overrepresented with age.
The results showed that NRM at 1 year was 13% for young patients, 20% for middle-age patients, and 33% for elderly patients (P less than .001). Overall survival at 3 years followed an inverse trend, decreasing with age from 60% in young patients to 54% in middle-age patients, before dropping more dramatically to 38% in the elderly (P less than .001).
In contrast to these significant associations between age and survival, relapse risk at 3 years remained relatively consistent, with young patients at 30%, middle-age patients at 31%, and elderly patients at 28% (P = .355).
The investigators noted that the risk of NRM increased most dramatically between middle age and old age, with less significant differences between the middle-age and young groups. They suggested that “age per se should have a limited impact on the indication for alloHCT for NHL in patients up to age 65 years.”
The increased risk with elderly status could not be fully explained by comorbidities, although these were more common in elderly patients. After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.” Therefore, age remains an independent risk factor.
“The information provided in this cohort of patients with NHL, the largest reported to date, is useful and relevant, especially in the era of evolving therapies,” the investigators wrote. They added that the information is “even more relevant now with the availability of treatment with ... chimeric antigen receptor (CAR) T cells ... after relapse post-alloHCT.”
The investigators reported having no financial disclosures.
SOURCE: Kyriakou C et al. Biol Blood Marrow Transplant. 2018 Sep 13. doi: 10.1016/j.bbmt.2018.08.025.
Elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within 1 year of allogeneic hematopoietic cell transplantation (alloHCT), compared with younger or middle-age patients, according to investigators.
Comorbidities also increased risks of nonrelapse mortality (NRM) at 1 year, but to a lesser extent than that of elderly status, reported lead author Charalampia Kyriakou, MD, PhD, of the department of haematology at University College London Hospital and London North West University Healthcare NHS Trust, and her colleagues.
“Although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group,” the investigators wrote in Biology of Blood and Marrow Transplantation.
This decision is becoming more common, they noted. “With the advent of reduced-intensity conditioning (RIC) strategies and other improvements in transplantation technology, alloHCT is being increasingly considered in elderly patients with [relapsed and refractory] NHL.”
The retrospective study analyzed 3,919 patients with NHL who underwent alloHCT between 2003 and 2013. Patients were sorted into three age groups: young (18-50 years), middle age (51-65 years), or elderly (66-77 years).
Disease types also were reported: 1,461 patients had follicular lymphoma (FL; 37%), 1,192 had diffuse large B cell lymphoma (DLBCL; 30%), 823 had mantle cell lymphoma (MCL; 21%), and 443 had peripheral T cell lymphoma (PTCL; 11%).
At the time of alloHCT, about 85% of patients were chemosensitive, with the remainder being chemorefractory. The age groups had similar patient characteristics, with exceptions noted for unrelated donors, MCL, and RIC, which became increasingly overrepresented with age.
The results showed that NRM at 1 year was 13% for young patients, 20% for middle-age patients, and 33% for elderly patients (P less than .001). Overall survival at 3 years followed an inverse trend, decreasing with age from 60% in young patients to 54% in middle-age patients, before dropping more dramatically to 38% in the elderly (P less than .001).
In contrast to these significant associations between age and survival, relapse risk at 3 years remained relatively consistent, with young patients at 30%, middle-age patients at 31%, and elderly patients at 28% (P = .355).
The investigators noted that the risk of NRM increased most dramatically between middle age and old age, with less significant differences between the middle-age and young groups. They suggested that “age per se should have a limited impact on the indication for alloHCT for NHL in patients up to age 65 years.”
The increased risk with elderly status could not be fully explained by comorbidities, although these were more common in elderly patients. After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.” Therefore, age remains an independent risk factor.
“The information provided in this cohort of patients with NHL, the largest reported to date, is useful and relevant, especially in the era of evolving therapies,” the investigators wrote. They added that the information is “even more relevant now with the availability of treatment with ... chimeric antigen receptor (CAR) T cells ... after relapse post-alloHCT.”
The investigators reported having no financial disclosures.
SOURCE: Kyriakou C et al. Biol Blood Marrow Transplant. 2018 Sep 13. doi: 10.1016/j.bbmt.2018.08.025.
Elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within 1 year of allogeneic hematopoietic cell transplantation (alloHCT), compared with younger or middle-age patients, according to investigators.
Comorbidities also increased risks of nonrelapse mortality (NRM) at 1 year, but to a lesser extent than that of elderly status, reported lead author Charalampia Kyriakou, MD, PhD, of the department of haematology at University College London Hospital and London North West University Healthcare NHS Trust, and her colleagues.
“Although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group,” the investigators wrote in Biology of Blood and Marrow Transplantation.
This decision is becoming more common, they noted. “With the advent of reduced-intensity conditioning (RIC) strategies and other improvements in transplantation technology, alloHCT is being increasingly considered in elderly patients with [relapsed and refractory] NHL.”
The retrospective study analyzed 3,919 patients with NHL who underwent alloHCT between 2003 and 2013. Patients were sorted into three age groups: young (18-50 years), middle age (51-65 years), or elderly (66-77 years).
Disease types also were reported: 1,461 patients had follicular lymphoma (FL; 37%), 1,192 had diffuse large B cell lymphoma (DLBCL; 30%), 823 had mantle cell lymphoma (MCL; 21%), and 443 had peripheral T cell lymphoma (PTCL; 11%).
At the time of alloHCT, about 85% of patients were chemosensitive, with the remainder being chemorefractory. The age groups had similar patient characteristics, with exceptions noted for unrelated donors, MCL, and RIC, which became increasingly overrepresented with age.
The results showed that NRM at 1 year was 13% for young patients, 20% for middle-age patients, and 33% for elderly patients (P less than .001). Overall survival at 3 years followed an inverse trend, decreasing with age from 60% in young patients to 54% in middle-age patients, before dropping more dramatically to 38% in the elderly (P less than .001).
In contrast to these significant associations between age and survival, relapse risk at 3 years remained relatively consistent, with young patients at 30%, middle-age patients at 31%, and elderly patients at 28% (P = .355).
The investigators noted that the risk of NRM increased most dramatically between middle age and old age, with less significant differences between the middle-age and young groups. They suggested that “age per se should have a limited impact on the indication for alloHCT for NHL in patients up to age 65 years.”
The increased risk with elderly status could not be fully explained by comorbidities, although these were more common in elderly patients. After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.” Therefore, age remains an independent risk factor.
“The information provided in this cohort of patients with NHL, the largest reported to date, is useful and relevant, especially in the era of evolving therapies,” the investigators wrote. They added that the information is “even more relevant now with the availability of treatment with ... chimeric antigen receptor (CAR) T cells ... after relapse post-alloHCT.”
The investigators reported having no financial disclosures.
SOURCE: Kyriakou C et al. Biol Blood Marrow Transplant. 2018 Sep 13. doi: 10.1016/j.bbmt.2018.08.025.
FROM BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Key clinical point:
Major finding: One-year nonrelapse mortality (NRM) was 13% for young patients, 20% for middle-age patients, and 33% for elderly patients (P less than .001).
Study details: A retrospective analysis of 3,919 patients with NHL who underwent alloHCT between 2003 and 2013.
Disclosures: The researchers reported having no financial disclosures.
Source: Kyriakou C et al. Biol Blood Marrow Transplant. 2018 Sep 13. doi: 10.1016/j.bbmt.2018.08.025.
Breast cancer in men comparable with women, gonadal therapy debated
MUNICH – Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate, according to recent trials and conference proceedings.
Male breast cancer is a rare, little-studied disease that was highlighted at the annual meeting of the European Society for Medical Oncology.
“This is a truly magnificent effort made by these authors,” said invited discussant Carolien Schroeder, MD, PhD, of the University Medical Center Groningen in the Netherlands, noting the challenges inherent to studies of niche cancer populations.
Previous studies have shown that men with MBC are usually hormone receptor positive (HR+) and older than women with MBC. Male patients also tend to present with more severe disease.
“[Male breast cancer patients] usually present with higher stages of disease; larger tumors, more nodal involvement, and more metastatic disease,” Dr. Schroeder said. “And 4%-16% may have genetic predisposition, usually due to a BRCA2 mutation.”
One retrospective study used data from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform to further knowledge of male patient characteristics, treatment types, and disease outcomes. ESME is a national database that stores patient information from 18 cancer centers in France.
“We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment,” said principal investigator Jean-Sébastien Frénel, MD, of the Institut de Cancérologie de l’Ouest in Nantes, France, in an interview.
The ESME study evaluated 16,701 patients with MBC: 16,552 women (99.11%) and 149 men (0.89%). Patients received at least one treatment between January 2008 and December 2014.
On average, male patients were older than females (mean: 68.1 years vs. 60.6 years), which lines up with existing data; in contrast, 78.4% of men were HR+, which is slightly lower than the widely described figure of 90%. Almost half of the HR+/human epidermal growth factor 2– (HER2–) male patients were given a frontline hormonal therapy (43%); of those, 44% received tamoxifen, 40% received an aromatase inhibitor (with or without a gonadotropin-releasing hormone analog [GnRH]), and 16% received other therapies. Outcomes were relatively similar between men and women: median progression-free survival (PFS) was 9.8 months for men, compared with 13.0 months for women. About one-quarter of HR+/HER2– men (27.6%) received frontline chemotherapy, resulting in a PFS of 6.9 months compared with 6.3 months for matched women. Overall survival was also slightly longer for men than matched women (41.8 months vs 34.9 months). In general, these statistics show that men and women received similar treatments and had similar outcomes.
“Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors,” Dr. Frénel said. “But few patients received aromatase inhibitors plus [GnRH] analogs despite some guidelines recommending that they should be given in combination.”
GnRH for men remains a topic of debate. Although aromatase inhibitors should be given with GnRH to avoid a negative feedback loop, gonadal suppression causes erectile dysfunction, thereby decreasing well-being. This dilemma is made worse by a lack of data on hormonal therapy for men with breast cancer.
To address this shortcoming, a prospective, randomized trial compared three different hormonal regimens for men. Male-GBG54 involved 55 men with breast cancer. For 6 months, patients received 1 of 3 treatment regimens: tamoxifen (20 mg/day), tamoxifen + GnRH (subcutaneous every 3 months), or exemestane (25 mg daily) + GnRH. Median estradiol levels were measured at 3 months and 6 months, and wellbeing was measured using questionnaires.
As expected, the results showed increased estradiol levels in the tamoxifen group and decreased levels in the GnRH group. Men were generally dissatisfied with GnRH therapy because of the erectile dysfunction it caused.
“Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients’ well-being and erectile function profoundly,” lead author Mattea Reinisch, MD, of Klinikum Essen-Mitte (Germany), said in an interview.
Dr. Schroeder agreed that tamoxifen should remain the standard treatment but suggested that the benefits of gonadal suppression may outweigh the downsides. “We need efficacy data for gonadal suppression,” she said. “After all, we are advising our premenopausal breast cancer patients to undergo the gonadal suppression therapy on a daily basis because of the oncological superiority, despite the toxicity they are also experiencing.”
Dr. Schroeder again called for efficacy data and described shortcomings of Male-GBG54: “[Dr. Reinisch and her colleagues] have chosen a biological surrogate endpoint, but what we’d really like, of course, [are] the efficacy data. The quality of life data are not breast-cancer specific, and these are only data for 6 months, whereas, particularly in the metastatic setting, the compliance issue after 6 months is also relevant.”
Reflecting on the data from ESME and Male-GBG54, Dr. Schroeder said, “I think this field is maturing, and intervention trials have proven themselves to be possible in this niche population.”
Looking to the future, Dr. Schroeder suggested that male breast cancer can be studied either in separate trials from women (focusing on sex-specific targets), or in shared studies, as many disease characteristics are the same regardless of sex. She also said that worse disease in men is likely due to delayed presentation rather than biological differences between men and women.
“This leaves room for improvement,” Dr. Schroeder said. “We still need to work on the awareness of this disease.”
Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
SOURCES: Sirieix J et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.
MUNICH – Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate, according to recent trials and conference proceedings.
Male breast cancer is a rare, little-studied disease that was highlighted at the annual meeting of the European Society for Medical Oncology.
“This is a truly magnificent effort made by these authors,” said invited discussant Carolien Schroeder, MD, PhD, of the University Medical Center Groningen in the Netherlands, noting the challenges inherent to studies of niche cancer populations.
Previous studies have shown that men with MBC are usually hormone receptor positive (HR+) and older than women with MBC. Male patients also tend to present with more severe disease.
“[Male breast cancer patients] usually present with higher stages of disease; larger tumors, more nodal involvement, and more metastatic disease,” Dr. Schroeder said. “And 4%-16% may have genetic predisposition, usually due to a BRCA2 mutation.”
One retrospective study used data from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform to further knowledge of male patient characteristics, treatment types, and disease outcomes. ESME is a national database that stores patient information from 18 cancer centers in France.
“We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment,” said principal investigator Jean-Sébastien Frénel, MD, of the Institut de Cancérologie de l’Ouest in Nantes, France, in an interview.
The ESME study evaluated 16,701 patients with MBC: 16,552 women (99.11%) and 149 men (0.89%). Patients received at least one treatment between January 2008 and December 2014.
On average, male patients were older than females (mean: 68.1 years vs. 60.6 years), which lines up with existing data; in contrast, 78.4% of men were HR+, which is slightly lower than the widely described figure of 90%. Almost half of the HR+/human epidermal growth factor 2– (HER2–) male patients were given a frontline hormonal therapy (43%); of those, 44% received tamoxifen, 40% received an aromatase inhibitor (with or without a gonadotropin-releasing hormone analog [GnRH]), and 16% received other therapies. Outcomes were relatively similar between men and women: median progression-free survival (PFS) was 9.8 months for men, compared with 13.0 months for women. About one-quarter of HR+/HER2– men (27.6%) received frontline chemotherapy, resulting in a PFS of 6.9 months compared with 6.3 months for matched women. Overall survival was also slightly longer for men than matched women (41.8 months vs 34.9 months). In general, these statistics show that men and women received similar treatments and had similar outcomes.
“Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors,” Dr. Frénel said. “But few patients received aromatase inhibitors plus [GnRH] analogs despite some guidelines recommending that they should be given in combination.”
GnRH for men remains a topic of debate. Although aromatase inhibitors should be given with GnRH to avoid a negative feedback loop, gonadal suppression causes erectile dysfunction, thereby decreasing well-being. This dilemma is made worse by a lack of data on hormonal therapy for men with breast cancer.
To address this shortcoming, a prospective, randomized trial compared three different hormonal regimens for men. Male-GBG54 involved 55 men with breast cancer. For 6 months, patients received 1 of 3 treatment regimens: tamoxifen (20 mg/day), tamoxifen + GnRH (subcutaneous every 3 months), or exemestane (25 mg daily) + GnRH. Median estradiol levels were measured at 3 months and 6 months, and wellbeing was measured using questionnaires.
As expected, the results showed increased estradiol levels in the tamoxifen group and decreased levels in the GnRH group. Men were generally dissatisfied with GnRH therapy because of the erectile dysfunction it caused.
“Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients’ well-being and erectile function profoundly,” lead author Mattea Reinisch, MD, of Klinikum Essen-Mitte (Germany), said in an interview.
Dr. Schroeder agreed that tamoxifen should remain the standard treatment but suggested that the benefits of gonadal suppression may outweigh the downsides. “We need efficacy data for gonadal suppression,” she said. “After all, we are advising our premenopausal breast cancer patients to undergo the gonadal suppression therapy on a daily basis because of the oncological superiority, despite the toxicity they are also experiencing.”
Dr. Schroeder again called for efficacy data and described shortcomings of Male-GBG54: “[Dr. Reinisch and her colleagues] have chosen a biological surrogate endpoint, but what we’d really like, of course, [are] the efficacy data. The quality of life data are not breast-cancer specific, and these are only data for 6 months, whereas, particularly in the metastatic setting, the compliance issue after 6 months is also relevant.”
Reflecting on the data from ESME and Male-GBG54, Dr. Schroeder said, “I think this field is maturing, and intervention trials have proven themselves to be possible in this niche population.”
Looking to the future, Dr. Schroeder suggested that male breast cancer can be studied either in separate trials from women (focusing on sex-specific targets), or in shared studies, as many disease characteristics are the same regardless of sex. She also said that worse disease in men is likely due to delayed presentation rather than biological differences between men and women.
“This leaves room for improvement,” Dr. Schroeder said. “We still need to work on the awareness of this disease.”
Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
SOURCES: Sirieix J et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.
MUNICH – Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate, according to recent trials and conference proceedings.
Male breast cancer is a rare, little-studied disease that was highlighted at the annual meeting of the European Society for Medical Oncology.
“This is a truly magnificent effort made by these authors,” said invited discussant Carolien Schroeder, MD, PhD, of the University Medical Center Groningen in the Netherlands, noting the challenges inherent to studies of niche cancer populations.
Previous studies have shown that men with MBC are usually hormone receptor positive (HR+) and older than women with MBC. Male patients also tend to present with more severe disease.
“[Male breast cancer patients] usually present with higher stages of disease; larger tumors, more nodal involvement, and more metastatic disease,” Dr. Schroeder said. “And 4%-16% may have genetic predisposition, usually due to a BRCA2 mutation.”
One retrospective study used data from the Epidemiological Strategy and Medical Economics Metastatic Breast Cancer (ESME MBC) platform to further knowledge of male patient characteristics, treatment types, and disease outcomes. ESME is a national database that stores patient information from 18 cancer centers in France.
“We have reported on one of the biggest series of men with metastatic disease, with comprehensive data on their management and outcome with different types of treatment,” said principal investigator Jean-Sébastien Frénel, MD, of the Institut de Cancérologie de l’Ouest in Nantes, France, in an interview.
The ESME study evaluated 16,701 patients with MBC: 16,552 women (99.11%) and 149 men (0.89%). Patients received at least one treatment between January 2008 and December 2014.
On average, male patients were older than females (mean: 68.1 years vs. 60.6 years), which lines up with existing data; in contrast, 78.4% of men were HR+, which is slightly lower than the widely described figure of 90%. Almost half of the HR+/human epidermal growth factor 2– (HER2–) male patients were given a frontline hormonal therapy (43%); of those, 44% received tamoxifen, 40% received an aromatase inhibitor (with or without a gonadotropin-releasing hormone analog [GnRH]), and 16% received other therapies. Outcomes were relatively similar between men and women: median progression-free survival (PFS) was 9.8 months for men, compared with 13.0 months for women. About one-quarter of HR+/HER2– men (27.6%) received frontline chemotherapy, resulting in a PFS of 6.9 months compared with 6.3 months for matched women. Overall survival was also slightly longer for men than matched women (41.8 months vs 34.9 months). In general, these statistics show that men and women received similar treatments and had similar outcomes.
“Most of the patients receiving hormonal therapy were treated with tamoxifen and the remainder received aromatase inhibitors,” Dr. Frénel said. “But few patients received aromatase inhibitors plus [GnRH] analogs despite some guidelines recommending that they should be given in combination.”
GnRH for men remains a topic of debate. Although aromatase inhibitors should be given with GnRH to avoid a negative feedback loop, gonadal suppression causes erectile dysfunction, thereby decreasing well-being. This dilemma is made worse by a lack of data on hormonal therapy for men with breast cancer.
To address this shortcoming, a prospective, randomized trial compared three different hormonal regimens for men. Male-GBG54 involved 55 men with breast cancer. For 6 months, patients received 1 of 3 treatment regimens: tamoxifen (20 mg/day), tamoxifen + GnRH (subcutaneous every 3 months), or exemestane (25 mg daily) + GnRH. Median estradiol levels were measured at 3 months and 6 months, and wellbeing was measured using questionnaires.
As expected, the results showed increased estradiol levels in the tamoxifen group and decreased levels in the GnRH group. Men were generally dissatisfied with GnRH therapy because of the erectile dysfunction it caused.
“Tamoxifen monotherapy should be kept as standard hormonal therapy for men with breast cancer. The side effects are moderate, hardly impairing sexual behavior. The combination with GnRH influenced patients’ well-being and erectile function profoundly,” lead author Mattea Reinisch, MD, of Klinikum Essen-Mitte (Germany), said in an interview.
Dr. Schroeder agreed that tamoxifen should remain the standard treatment but suggested that the benefits of gonadal suppression may outweigh the downsides. “We need efficacy data for gonadal suppression,” she said. “After all, we are advising our premenopausal breast cancer patients to undergo the gonadal suppression therapy on a daily basis because of the oncological superiority, despite the toxicity they are also experiencing.”
Dr. Schroeder again called for efficacy data and described shortcomings of Male-GBG54: “[Dr. Reinisch and her colleagues] have chosen a biological surrogate endpoint, but what we’d really like, of course, [are] the efficacy data. The quality of life data are not breast-cancer specific, and these are only data for 6 months, whereas, particularly in the metastatic setting, the compliance issue after 6 months is also relevant.”
Reflecting on the data from ESME and Male-GBG54, Dr. Schroeder said, “I think this field is maturing, and intervention trials have proven themselves to be possible in this niche population.”
Looking to the future, Dr. Schroeder suggested that male breast cancer can be studied either in separate trials from women (focusing on sex-specific targets), or in shared studies, as many disease characteristics are the same regardless of sex. She also said that worse disease in men is likely due to delayed presentation rather than biological differences between men and women.
“This leaves room for improvement,” Dr. Schroeder said. “We still need to work on the awareness of this disease.”
Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
SOURCES: Sirieix J et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.
REPORTING FROM ESMO 2018
Key clinical point: Men with metastatic breast cancer (MBC) have a similar prognosis, compared with women, but gonadal suppression remains a topic of debate.
Major finding: Median PFS was 9.8 months in men, compared with 13.0 months in matched women.
Study details: The ESME study was a large-scale retrospective analysis of 16,701 patients, 149 of whom were men with MBC. Male-GBG54 was a prospective, randomized trial involving 46 MBC patients who received three different endocrine therapies.
Disclosures: Discussant Dr. Schroeder disclosed financial relationships with Novartis, Roche, Genentech, and others. Male-GBG54 was funded by Claudia von Schilling Foundation.
Source: Sirieix et al. ESMO 2018, Abstract 294PD; Reinisch et al. ESMO 2018, Abstract 273PD.