User login
ARAMIS: Darolutamide shines in nonmetastatic CRPC
SAN FRANCISCO – Darolutamide, a novel investigational antiandrogen agent, is efficacious and well tolerated when used to treat nonmetastatic, castration-resistant prostate cancer (nmCRPC), according to results of the phase 3, randomized, controlled ARAMIS trial.
“In men with high-risk M0 CRPC, two next-generation androgen receptor inhibitors, namely, enzalutamide (Xtandi) and apalutamide (Erleada), were recently shown to improve metastasis-free survival, although they were associated with increased cognitive impairment, falls, and other side effects,” commented lead investigator Karim Fizazi, MD, PhD, head of the department of cancer medicine at the Institut Gustave Roussy in Paris. “Enzalutamide and apalutamide are chemically very similar, while darolutamide is structurally distinct. Also, darolutamide does not cross the blood-brain barrier, which may result in less CNS-related side effects.”
ARAMIS enrolled 1,509 men with nmCRPC who had a prostate-specific antigen (PSA) doubling time of 10 months or less and were on and continued androgen deprivation therapy. The men were randomized 2:1 to receive darolutamide or placebo.
With a median follow-up of 17.9 months, median metastasis-free survival was almost 2 years longer with darolutamide, corresponding to a 59% reduction in the risk of distant metastases or death, relative to placebo, according to results reported at the symposium and simultaneously published in the New England Journal of Medicine (2019 Feb 14. doi: 10.1056/NEJMoa1815671). There was also a 29% reduction in risk of death (in an interim analysis), a 35% reduction in risk of pain progression, and 57% reductions each in need for chemotherapy and first symptomatic skeletal events. Meanwhile, the drug had a good safety and tolerability profile, with rates and types of events similar to those seen with placebo.
“We believe that darolutamide should become a new standard of care for men with high-risk nmCRPC,” Dr. Fizazi concluded.
Practice-changing results?
The ARAMIS findings meet some – but not all – of a set of criteria that would support a change in current practice to using darolutamide, according to invited discussant Ian D. Davis, MBBS, PhD, a professor at Monash University, Melbourne.
The first criterion, whether the disease is a condition needing treatment, is likely met, as 69% of patients had a PSA doubling time of 6 months or less, and previous research suggests that this subset, at least, has high risk for bone metastases or death.
A second criterion is whether metastasis-free survival is a meaningful endpoint. “It is according to the FDA [Food and Drug Administration],” Dr. Davis said, noting that they now accept it as a registrable endpoint in nmCRPC if it is supported by positive secondary endpoints. “But are we talking about a sensitivity question here, is M0 a rapidly disappearing condition,” given that new imaging technologies often do reveal metastases in this population? “And is metastasis-free survival truly a surrogate for overall survival? I think those questions are still open, and we need to use our own judgment.”
Darolutamide appears to have acceptable toxicity, a third criterion, but information regarding its impact on subsequent treatment efficacy, a fourth criterion, is still lacking.
The fifth and final criterion, cost-effectiveness, can be assessed using the incremental cost-effectiveness ratio. But because overall survival benefit and price of darolutamide are still unknown, calculations of cost per life-year saved are not yet possible.
“So at the moment, I think it’s unclear whether ARAMIS should change practice,” Dr. Davis concluded. “I would certainly be prepared to change my conclusions on this with more information and further follow-up.”
Study details
The men randomized in ARAMIS had a median PSA doubling time of roughly 4.5 months, Dr. Fizazi reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Only about 5% were receiving a bone-sparing agent.
Median metastasis-free survival was 40.4 months with darolutamide and 18.4 months with placebo (hazard ratio, 0.41; P less than .0001). Benefit was similar across a range of subgroups.
In an interim analysis, median overall survival was not reached in either group, but the 3-year rate was 83% with darolutamide and 73% with placebo (hazard ratio, 0.71; P = .0452). The drug also was superior in terms of progression-free survival (36.8 vs. 14.8 months; HR, 0.38; P less than .0001), time to pain progression (40.3 vs. 25.4 months; HR, 0.65; P less than .0001), time to cytotoxic chemotherapy (not reached vs. 38.2 months; HR, 0.43; P less than .0001), and time to first symptomatic skeletal event (not reached in either group; HR, 0.43; P = .0113).
Patients in the darolutamide and placebo groups had similar rates of treatment discontinuation because of any-grade treatment-emergent adverse events (8.9% vs. 8.7%) and because of grade 3 or 4 treatment-emergent adverse events (3.3% vs. 4.3%). The former had a higher rate of any-grade fatigue/asthenia (15.8% vs. 11.4%), but this difference was no longer evident after adjustment for duration of exposure, according to Dr. Fizazi. Notably, the groups were similar on rates of bone fractures, falls, cognitive disorders, seizures, hypertension, and coronary artery disorders.
Finally, darolutamide was also associated with better health-related quality of life, with men in that group having lower scores for pain interference, pain severity, and urinary symptoms (P less than .01 for all).
Dr. Fizazi reported that he receives honoraria from Astellas Pharma, Janssen, Merck, and Sanofi; that he has a consulting or advisory role with Amgen, Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, CureVac, ESSA, Janssen Oncology, Orion Pharma, Roche/Genentech, and Sanofi; and that he receives travel, accommodations, and/or expenses from Amgen and Janssen. The trial was sponsored by Bayer.
SOURCE: Fizazi K et al. GUCS 2019, Abstract 140.
SAN FRANCISCO – Darolutamide, a novel investigational antiandrogen agent, is efficacious and well tolerated when used to treat nonmetastatic, castration-resistant prostate cancer (nmCRPC), according to results of the phase 3, randomized, controlled ARAMIS trial.
“In men with high-risk M0 CRPC, two next-generation androgen receptor inhibitors, namely, enzalutamide (Xtandi) and apalutamide (Erleada), were recently shown to improve metastasis-free survival, although they were associated with increased cognitive impairment, falls, and other side effects,” commented lead investigator Karim Fizazi, MD, PhD, head of the department of cancer medicine at the Institut Gustave Roussy in Paris. “Enzalutamide and apalutamide are chemically very similar, while darolutamide is structurally distinct. Also, darolutamide does not cross the blood-brain barrier, which may result in less CNS-related side effects.”
ARAMIS enrolled 1,509 men with nmCRPC who had a prostate-specific antigen (PSA) doubling time of 10 months or less and were on and continued androgen deprivation therapy. The men were randomized 2:1 to receive darolutamide or placebo.
With a median follow-up of 17.9 months, median metastasis-free survival was almost 2 years longer with darolutamide, corresponding to a 59% reduction in the risk of distant metastases or death, relative to placebo, according to results reported at the symposium and simultaneously published in the New England Journal of Medicine (2019 Feb 14. doi: 10.1056/NEJMoa1815671). There was also a 29% reduction in risk of death (in an interim analysis), a 35% reduction in risk of pain progression, and 57% reductions each in need for chemotherapy and first symptomatic skeletal events. Meanwhile, the drug had a good safety and tolerability profile, with rates and types of events similar to those seen with placebo.
“We believe that darolutamide should become a new standard of care for men with high-risk nmCRPC,” Dr. Fizazi concluded.
Practice-changing results?
The ARAMIS findings meet some – but not all – of a set of criteria that would support a change in current practice to using darolutamide, according to invited discussant Ian D. Davis, MBBS, PhD, a professor at Monash University, Melbourne.
The first criterion, whether the disease is a condition needing treatment, is likely met, as 69% of patients had a PSA doubling time of 6 months or less, and previous research suggests that this subset, at least, has high risk for bone metastases or death.
A second criterion is whether metastasis-free survival is a meaningful endpoint. “It is according to the FDA [Food and Drug Administration],” Dr. Davis said, noting that they now accept it as a registrable endpoint in nmCRPC if it is supported by positive secondary endpoints. “But are we talking about a sensitivity question here, is M0 a rapidly disappearing condition,” given that new imaging technologies often do reveal metastases in this population? “And is metastasis-free survival truly a surrogate for overall survival? I think those questions are still open, and we need to use our own judgment.”
Darolutamide appears to have acceptable toxicity, a third criterion, but information regarding its impact on subsequent treatment efficacy, a fourth criterion, is still lacking.
The fifth and final criterion, cost-effectiveness, can be assessed using the incremental cost-effectiveness ratio. But because overall survival benefit and price of darolutamide are still unknown, calculations of cost per life-year saved are not yet possible.
“So at the moment, I think it’s unclear whether ARAMIS should change practice,” Dr. Davis concluded. “I would certainly be prepared to change my conclusions on this with more information and further follow-up.”
Study details
The men randomized in ARAMIS had a median PSA doubling time of roughly 4.5 months, Dr. Fizazi reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Only about 5% were receiving a bone-sparing agent.
Median metastasis-free survival was 40.4 months with darolutamide and 18.4 months with placebo (hazard ratio, 0.41; P less than .0001). Benefit was similar across a range of subgroups.
In an interim analysis, median overall survival was not reached in either group, but the 3-year rate was 83% with darolutamide and 73% with placebo (hazard ratio, 0.71; P = .0452). The drug also was superior in terms of progression-free survival (36.8 vs. 14.8 months; HR, 0.38; P less than .0001), time to pain progression (40.3 vs. 25.4 months; HR, 0.65; P less than .0001), time to cytotoxic chemotherapy (not reached vs. 38.2 months; HR, 0.43; P less than .0001), and time to first symptomatic skeletal event (not reached in either group; HR, 0.43; P = .0113).
Patients in the darolutamide and placebo groups had similar rates of treatment discontinuation because of any-grade treatment-emergent adverse events (8.9% vs. 8.7%) and because of grade 3 or 4 treatment-emergent adverse events (3.3% vs. 4.3%). The former had a higher rate of any-grade fatigue/asthenia (15.8% vs. 11.4%), but this difference was no longer evident after adjustment for duration of exposure, according to Dr. Fizazi. Notably, the groups were similar on rates of bone fractures, falls, cognitive disorders, seizures, hypertension, and coronary artery disorders.
Finally, darolutamide was also associated with better health-related quality of life, with men in that group having lower scores for pain interference, pain severity, and urinary symptoms (P less than .01 for all).
Dr. Fizazi reported that he receives honoraria from Astellas Pharma, Janssen, Merck, and Sanofi; that he has a consulting or advisory role with Amgen, Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, CureVac, ESSA, Janssen Oncology, Orion Pharma, Roche/Genentech, and Sanofi; and that he receives travel, accommodations, and/or expenses from Amgen and Janssen. The trial was sponsored by Bayer.
SOURCE: Fizazi K et al. GUCS 2019, Abstract 140.
SAN FRANCISCO – Darolutamide, a novel investigational antiandrogen agent, is efficacious and well tolerated when used to treat nonmetastatic, castration-resistant prostate cancer (nmCRPC), according to results of the phase 3, randomized, controlled ARAMIS trial.
“In men with high-risk M0 CRPC, two next-generation androgen receptor inhibitors, namely, enzalutamide (Xtandi) and apalutamide (Erleada), were recently shown to improve metastasis-free survival, although they were associated with increased cognitive impairment, falls, and other side effects,” commented lead investigator Karim Fizazi, MD, PhD, head of the department of cancer medicine at the Institut Gustave Roussy in Paris. “Enzalutamide and apalutamide are chemically very similar, while darolutamide is structurally distinct. Also, darolutamide does not cross the blood-brain barrier, which may result in less CNS-related side effects.”
ARAMIS enrolled 1,509 men with nmCRPC who had a prostate-specific antigen (PSA) doubling time of 10 months or less and were on and continued androgen deprivation therapy. The men were randomized 2:1 to receive darolutamide or placebo.
With a median follow-up of 17.9 months, median metastasis-free survival was almost 2 years longer with darolutamide, corresponding to a 59% reduction in the risk of distant metastases or death, relative to placebo, according to results reported at the symposium and simultaneously published in the New England Journal of Medicine (2019 Feb 14. doi: 10.1056/NEJMoa1815671). There was also a 29% reduction in risk of death (in an interim analysis), a 35% reduction in risk of pain progression, and 57% reductions each in need for chemotherapy and first symptomatic skeletal events. Meanwhile, the drug had a good safety and tolerability profile, with rates and types of events similar to those seen with placebo.
“We believe that darolutamide should become a new standard of care for men with high-risk nmCRPC,” Dr. Fizazi concluded.
Practice-changing results?
The ARAMIS findings meet some – but not all – of a set of criteria that would support a change in current practice to using darolutamide, according to invited discussant Ian D. Davis, MBBS, PhD, a professor at Monash University, Melbourne.
The first criterion, whether the disease is a condition needing treatment, is likely met, as 69% of patients had a PSA doubling time of 6 months or less, and previous research suggests that this subset, at least, has high risk for bone metastases or death.
A second criterion is whether metastasis-free survival is a meaningful endpoint. “It is according to the FDA [Food and Drug Administration],” Dr. Davis said, noting that they now accept it as a registrable endpoint in nmCRPC if it is supported by positive secondary endpoints. “But are we talking about a sensitivity question here, is M0 a rapidly disappearing condition,” given that new imaging technologies often do reveal metastases in this population? “And is metastasis-free survival truly a surrogate for overall survival? I think those questions are still open, and we need to use our own judgment.”
Darolutamide appears to have acceptable toxicity, a third criterion, but information regarding its impact on subsequent treatment efficacy, a fourth criterion, is still lacking.
The fifth and final criterion, cost-effectiveness, can be assessed using the incremental cost-effectiveness ratio. But because overall survival benefit and price of darolutamide are still unknown, calculations of cost per life-year saved are not yet possible.
“So at the moment, I think it’s unclear whether ARAMIS should change practice,” Dr. Davis concluded. “I would certainly be prepared to change my conclusions on this with more information and further follow-up.”
Study details
The men randomized in ARAMIS had a median PSA doubling time of roughly 4.5 months, Dr. Fizazi reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Only about 5% were receiving a bone-sparing agent.
Median metastasis-free survival was 40.4 months with darolutamide and 18.4 months with placebo (hazard ratio, 0.41; P less than .0001). Benefit was similar across a range of subgroups.
In an interim analysis, median overall survival was not reached in either group, but the 3-year rate was 83% with darolutamide and 73% with placebo (hazard ratio, 0.71; P = .0452). The drug also was superior in terms of progression-free survival (36.8 vs. 14.8 months; HR, 0.38; P less than .0001), time to pain progression (40.3 vs. 25.4 months; HR, 0.65; P less than .0001), time to cytotoxic chemotherapy (not reached vs. 38.2 months; HR, 0.43; P less than .0001), and time to first symptomatic skeletal event (not reached in either group; HR, 0.43; P = .0113).
Patients in the darolutamide and placebo groups had similar rates of treatment discontinuation because of any-grade treatment-emergent adverse events (8.9% vs. 8.7%) and because of grade 3 or 4 treatment-emergent adverse events (3.3% vs. 4.3%). The former had a higher rate of any-grade fatigue/asthenia (15.8% vs. 11.4%), but this difference was no longer evident after adjustment for duration of exposure, according to Dr. Fizazi. Notably, the groups were similar on rates of bone fractures, falls, cognitive disorders, seizures, hypertension, and coronary artery disorders.
Finally, darolutamide was also associated with better health-related quality of life, with men in that group having lower scores for pain interference, pain severity, and urinary symptoms (P less than .01 for all).
Dr. Fizazi reported that he receives honoraria from Astellas Pharma, Janssen, Merck, and Sanofi; that he has a consulting or advisory role with Amgen, Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, CureVac, ESSA, Janssen Oncology, Orion Pharma, Roche/Genentech, and Sanofi; and that he receives travel, accommodations, and/or expenses from Amgen and Janssen. The trial was sponsored by Bayer.
SOURCE: Fizazi K et al. GUCS 2019, Abstract 140.
REPORTING FROM GUCS 2019
Survival of patients with mCRPC on hormone therapy differs by race
SAN FRANCISCO – When given the same hormonal therapy for chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), African American men live about 4 months longer than do white men, finds a retrospective cohort study being reported at the 2019 Genitourinary Cancers Symposium.
“We know that African American men have a higher risk of mCRPC and worse survival than white men,” said lead study author Megan McNamara, MD, of Duke University, Durham, N.C. “However, despite this, there is also evidence to suggest that African Americans with advanced prostate cancer actually have better outcomes in response to several prostate cancer treatments compared to Caucasians.”
She and her colleagues analyzed data from the Veterans Health Administration database for a 5-year period (2013-2018), focusing on 2,123 white and 787 African American male veterans with chemotherapy-naive mCRPC who were treated with the anti-androgen abiraterone (Zytiga) or the androgen receptor inhibitor enzalutamide (Xtandi). Overall survival was measured from the first prescription claim for either drug following medical or surgical castration.
Main results reported in a presscast leading up to the symposium showed that with a median follow-up of about 1.6 years, median overall survival was 30 months for African American men, compared with 26 months for white men. The difference corresponded to a significantly lower risk of death for African American men in both univariate analysis (hazard ratio, 0.887; P = .0435) and multivariate analysis adjusted for age and comorbidities (HR, 0.826; P = .0020).
“When controlling for access to care through a single-payer system – in this case, the VA Health System – in chemotherapy-naive mCRPC patients, African Americans may have better overall survival than Caucasians when treated with abiraterone or enzalutamide,” Dr. McNamara summarized. “These results are consistent with what we have seen in prior studies in this population involving docetaxel (Taxotere), sipuleucel-T (Provenge), and abiraterone.”
Importantly, the data expand on previous findings for abiraterone in the Abi Race study, she noted. That study established that African American men had a better prostate-specific antigen (PSA) response to the drug (J Clin Oncol. 2018 Jun 7. doi: 10.1200/JCO.2018.36.18_suppl.LBA5009).
The new findings do not alter but rather reinforce current clinical practice, according to Dr. McNamara. “These are standard-of-care treatments, and it’s important that we have real-world studies that show that the standard-of-care treatments really work,” she elaborated. “So I don’t think that they necessarily change what we are doing. But they reinforce what we are already doing, and that it’s important that we make sure that every African American who is eligible for these medicines gets them.
“Our study is retrospective,” she acknowledged. “But it emphasizes the need for prospective trials in order to validate these findings and in order to try to understand the mechanism that underlies these differences in survival outcomes between African Americans and Caucasians with mCRPC when treated with these novel hormone therapies.”
The data are “very provocative, and it adds to an emerging database that if confirmed prospectively, really changes the way we think about racial differences,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
Full results of the study will be reported at the symposium, which is sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Dr. McNamara disclosed that she receives travel, accommodations, and/or expenses from Clovis Oncology; honoraria from Bayer and Exelixis; and research funding (institutional) from Bayer, Seattle Genetics/Astellas, Agensys, Clovis Oncology, and Janssen. The study was funded by Pfizer.
SOURCE: McNamara MA et al. Abstract 212.
SAN FRANCISCO – When given the same hormonal therapy for chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), African American men live about 4 months longer than do white men, finds a retrospective cohort study being reported at the 2019 Genitourinary Cancers Symposium.
“We know that African American men have a higher risk of mCRPC and worse survival than white men,” said lead study author Megan McNamara, MD, of Duke University, Durham, N.C. “However, despite this, there is also evidence to suggest that African Americans with advanced prostate cancer actually have better outcomes in response to several prostate cancer treatments compared to Caucasians.”
She and her colleagues analyzed data from the Veterans Health Administration database for a 5-year period (2013-2018), focusing on 2,123 white and 787 African American male veterans with chemotherapy-naive mCRPC who were treated with the anti-androgen abiraterone (Zytiga) or the androgen receptor inhibitor enzalutamide (Xtandi). Overall survival was measured from the first prescription claim for either drug following medical or surgical castration.
Main results reported in a presscast leading up to the symposium showed that with a median follow-up of about 1.6 years, median overall survival was 30 months for African American men, compared with 26 months for white men. The difference corresponded to a significantly lower risk of death for African American men in both univariate analysis (hazard ratio, 0.887; P = .0435) and multivariate analysis adjusted for age and comorbidities (HR, 0.826; P = .0020).
“When controlling for access to care through a single-payer system – in this case, the VA Health System – in chemotherapy-naive mCRPC patients, African Americans may have better overall survival than Caucasians when treated with abiraterone or enzalutamide,” Dr. McNamara summarized. “These results are consistent with what we have seen in prior studies in this population involving docetaxel (Taxotere), sipuleucel-T (Provenge), and abiraterone.”
Importantly, the data expand on previous findings for abiraterone in the Abi Race study, she noted. That study established that African American men had a better prostate-specific antigen (PSA) response to the drug (J Clin Oncol. 2018 Jun 7. doi: 10.1200/JCO.2018.36.18_suppl.LBA5009).
The new findings do not alter but rather reinforce current clinical practice, according to Dr. McNamara. “These are standard-of-care treatments, and it’s important that we have real-world studies that show that the standard-of-care treatments really work,” she elaborated. “So I don’t think that they necessarily change what we are doing. But they reinforce what we are already doing, and that it’s important that we make sure that every African American who is eligible for these medicines gets them.
“Our study is retrospective,” she acknowledged. “But it emphasizes the need for prospective trials in order to validate these findings and in order to try to understand the mechanism that underlies these differences in survival outcomes between African Americans and Caucasians with mCRPC when treated with these novel hormone therapies.”
The data are “very provocative, and it adds to an emerging database that if confirmed prospectively, really changes the way we think about racial differences,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
Full results of the study will be reported at the symposium, which is sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Dr. McNamara disclosed that she receives travel, accommodations, and/or expenses from Clovis Oncology; honoraria from Bayer and Exelixis; and research funding (institutional) from Bayer, Seattle Genetics/Astellas, Agensys, Clovis Oncology, and Janssen. The study was funded by Pfizer.
SOURCE: McNamara MA et al. Abstract 212.
SAN FRANCISCO – When given the same hormonal therapy for chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), African American men live about 4 months longer than do white men, finds a retrospective cohort study being reported at the 2019 Genitourinary Cancers Symposium.
“We know that African American men have a higher risk of mCRPC and worse survival than white men,” said lead study author Megan McNamara, MD, of Duke University, Durham, N.C. “However, despite this, there is also evidence to suggest that African Americans with advanced prostate cancer actually have better outcomes in response to several prostate cancer treatments compared to Caucasians.”
She and her colleagues analyzed data from the Veterans Health Administration database for a 5-year period (2013-2018), focusing on 2,123 white and 787 African American male veterans with chemotherapy-naive mCRPC who were treated with the anti-androgen abiraterone (Zytiga) or the androgen receptor inhibitor enzalutamide (Xtandi). Overall survival was measured from the first prescription claim for either drug following medical or surgical castration.
Main results reported in a presscast leading up to the symposium showed that with a median follow-up of about 1.6 years, median overall survival was 30 months for African American men, compared with 26 months for white men. The difference corresponded to a significantly lower risk of death for African American men in both univariate analysis (hazard ratio, 0.887; P = .0435) and multivariate analysis adjusted for age and comorbidities (HR, 0.826; P = .0020).
“When controlling for access to care through a single-payer system – in this case, the VA Health System – in chemotherapy-naive mCRPC patients, African Americans may have better overall survival than Caucasians when treated with abiraterone or enzalutamide,” Dr. McNamara summarized. “These results are consistent with what we have seen in prior studies in this population involving docetaxel (Taxotere), sipuleucel-T (Provenge), and abiraterone.”
Importantly, the data expand on previous findings for abiraterone in the Abi Race study, she noted. That study established that African American men had a better prostate-specific antigen (PSA) response to the drug (J Clin Oncol. 2018 Jun 7. doi: 10.1200/JCO.2018.36.18_suppl.LBA5009).
The new findings do not alter but rather reinforce current clinical practice, according to Dr. McNamara. “These are standard-of-care treatments, and it’s important that we have real-world studies that show that the standard-of-care treatments really work,” she elaborated. “So I don’t think that they necessarily change what we are doing. But they reinforce what we are already doing, and that it’s important that we make sure that every African American who is eligible for these medicines gets them.
“Our study is retrospective,” she acknowledged. “But it emphasizes the need for prospective trials in order to validate these findings and in order to try to understand the mechanism that underlies these differences in survival outcomes between African Americans and Caucasians with mCRPC when treated with these novel hormone therapies.”
The data are “very provocative, and it adds to an emerging database that if confirmed prospectively, really changes the way we think about racial differences,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
Full results of the study will be reported at the symposium, which is sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Dr. McNamara disclosed that she receives travel, accommodations, and/or expenses from Clovis Oncology; honoraria from Bayer and Exelixis; and research funding (institutional) from Bayer, Seattle Genetics/Astellas, Agensys, Clovis Oncology, and Janssen. The study was funded by Pfizer.
SOURCE: McNamara MA et al. Abstract 212.
REPORTING FROM GUCS 2019
Key clinical point: Benefit of contemporary hormone therapy for mCRPC may vary by race.
Major finding: Median overall survival on hormone therapy was 30 months for African American men versus 26 months for white men (adjusted hazard ratio, 0.826; P = .0020).
Study details: A retrospective cohort study of 2,123 white and 787 African American male veterans with chemotherapy-naive mCRPC treated with abiraterone or enzalutamide.
Disclosures: Dr. McNamara disclosed that she receives travel, accommodations, and/or expenses from Clovis Oncology; honoraria from Bayer and Exelixis; and research funding (institutional) from Bayer, Seattle Genetics/Astellas, Agensys, Clovis Oncology, and Janssen. The study was funded by Pfizer.
Source: McNamara MA et al. GUCS 2019, Abstract 212.
Pembrolizumab-axitinib nearly halves risk of death in RCC
SAN FRANCISCO – When used as first-line therapy for renal cell carcinoma (RCC), the combination of pembrolizumab and axitinib has similar safety and better efficacy than single-agent sunitinib, the current standard of care, according to findings of the KEYNOTE-426 trial that will be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.
“Axitinib is usually licensed and usually used in sunitinib-refractory disease. However, there is data for both pembrolizumab and axitinib in the frontline setting,” said lead author Thomas Powles, MBBS, MRCP, MD, of Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, and Queen Mary University of London. A phase 1b trial testing the combination showed an impressive 73% objective response rate and acceptable toxicity (Lancet Oncol. 2018;19:405-15), prompting further investigation.
The 861 patients in KEYNOTE-426, a phase 3, randomized, controlled trial, were evenly assigned to combination therapy with the immune checkpoint inhibitor pembrolizumab (Keytruda), which targets programmed death–1, plus the tyrosine kinase inhibitor axitinib (Inlyta), which targets vascular endothelial growth factor and platelet-derived growth factor, or to monotherapy with the tyrosine kinase inhibitor sunitinib (Sutent), which also targets those growth factors.
Main results reported in a presscast held before the symposium showed that, with a median follow-up of 12.8 months, pembrolizumab-axitinib reduced the risk of progression-free survival events by a relative 31% and the risk of death by a relative 47%, compared with sunitinib. The combination had a rate of grade 3-5 treatment-related adverse events similar to the rate with sunitinib alone.
“The benefit of pembrolizumab plus axitinib was seen irrespective of IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk group or PD-L1 [programmed death–ligand 1] status,” Dr. Powles noted. “Pembrolizumab and axitinib should be a standard of care in this setting, in my opinion.”
“This is a very significant trial, and it’s going to impact on patient management going forward, as it works through the regulatory process,” commented ASCO Expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, who is also deputy director and associate director of clinical research at the University of Virginia Cancer Center and a professor of medicine and urology at the University of Virginia, Charlottesville.
Study details
Patients in KEYNOTE-426 had newly diagnosed or recurrent stage IV clear cell RCC and had not received any previous systemic treatment for their advanced disease. They were randomized to pembrolizumab (200 mg intravenously every 3 weeks up to 35 cycles) plus axitinib (5 mg orally twice daily), or to sunitinib (50 mg orally once daily for first 4 weeks of each 6-week cycle).
Median overall survival was not reached in either group, but the 12-month rate was 89.9% with pembrolizumab-axitinib versus 78.3% with sunitinib, Dr. Powles reported in the presscast. The difference corresponded to a near halving of the risk of death with the combination (hazard ratio, 0.53; P less than .0001).
Median progression-free survival was 15.1 months with pembrolizumab-axitinib and 11.1 months with sunitinib. The difference corresponded to a nearly one-third reduction in the risk of events with the combination (HR, 0.69; P = .0001). “The 11.1 months is quite long for a control arm, so there’s nothing from these data to suggest that sunitinib underperformed in this trial,” he noted.
Pembrolizumab-axitinib was also associated with a higher objective response rate (59.3% vs. 35.7%; P less than .0001). The median duration of response was not reached with the former, compared with 15.2 months with the latter.
“Pembrolizumab and axitinib had a manageable safety profile,” Dr. Powles said. The rate of grade 3-5 treatment-related adverse events was 62.9% with the combination and 58.1% with sunitinib monotherapy.
The rate of events leading to death was similar at 0.9% and 1.6%, respectively. The rate of events leading to discontinuation of any treatment was 25.9% for pembrolizumab-axitinib and 10.1% for sunitinib, and the rate of events leading to discontinuation of both drugs in the combination was 8.2%.
Dr. Powles reported that he has a consulting or advisory role with Genentech/Roche, Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; has a nonspecified relationship with Ipsen and Bristol-Myers Squibb; receives honoraria from Roche/Genentech, Bristol-Myers Squibb, and Merck; and receives research funding from Astra-Zeneca/MedImmune and Roche/Genentech. The study was funded by Merck.
SOURCE: Powles T et al. GUCS 2019, Abstract 543.
SAN FRANCISCO – When used as first-line therapy for renal cell carcinoma (RCC), the combination of pembrolizumab and axitinib has similar safety and better efficacy than single-agent sunitinib, the current standard of care, according to findings of the KEYNOTE-426 trial that will be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.
“Axitinib is usually licensed and usually used in sunitinib-refractory disease. However, there is data for both pembrolizumab and axitinib in the frontline setting,” said lead author Thomas Powles, MBBS, MRCP, MD, of Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, and Queen Mary University of London. A phase 1b trial testing the combination showed an impressive 73% objective response rate and acceptable toxicity (Lancet Oncol. 2018;19:405-15), prompting further investigation.
The 861 patients in KEYNOTE-426, a phase 3, randomized, controlled trial, were evenly assigned to combination therapy with the immune checkpoint inhibitor pembrolizumab (Keytruda), which targets programmed death–1, plus the tyrosine kinase inhibitor axitinib (Inlyta), which targets vascular endothelial growth factor and platelet-derived growth factor, or to monotherapy with the tyrosine kinase inhibitor sunitinib (Sutent), which also targets those growth factors.
Main results reported in a presscast held before the symposium showed that, with a median follow-up of 12.8 months, pembrolizumab-axitinib reduced the risk of progression-free survival events by a relative 31% and the risk of death by a relative 47%, compared with sunitinib. The combination had a rate of grade 3-5 treatment-related adverse events similar to the rate with sunitinib alone.
“The benefit of pembrolizumab plus axitinib was seen irrespective of IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk group or PD-L1 [programmed death–ligand 1] status,” Dr. Powles noted. “Pembrolizumab and axitinib should be a standard of care in this setting, in my opinion.”
“This is a very significant trial, and it’s going to impact on patient management going forward, as it works through the regulatory process,” commented ASCO Expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, who is also deputy director and associate director of clinical research at the University of Virginia Cancer Center and a professor of medicine and urology at the University of Virginia, Charlottesville.
Study details
Patients in KEYNOTE-426 had newly diagnosed or recurrent stage IV clear cell RCC and had not received any previous systemic treatment for their advanced disease. They were randomized to pembrolizumab (200 mg intravenously every 3 weeks up to 35 cycles) plus axitinib (5 mg orally twice daily), or to sunitinib (50 mg orally once daily for first 4 weeks of each 6-week cycle).
Median overall survival was not reached in either group, but the 12-month rate was 89.9% with pembrolizumab-axitinib versus 78.3% with sunitinib, Dr. Powles reported in the presscast. The difference corresponded to a near halving of the risk of death with the combination (hazard ratio, 0.53; P less than .0001).
Median progression-free survival was 15.1 months with pembrolizumab-axitinib and 11.1 months with sunitinib. The difference corresponded to a nearly one-third reduction in the risk of events with the combination (HR, 0.69; P = .0001). “The 11.1 months is quite long for a control arm, so there’s nothing from these data to suggest that sunitinib underperformed in this trial,” he noted.
Pembrolizumab-axitinib was also associated with a higher objective response rate (59.3% vs. 35.7%; P less than .0001). The median duration of response was not reached with the former, compared with 15.2 months with the latter.
“Pembrolizumab and axitinib had a manageable safety profile,” Dr. Powles said. The rate of grade 3-5 treatment-related adverse events was 62.9% with the combination and 58.1% with sunitinib monotherapy.
The rate of events leading to death was similar at 0.9% and 1.6%, respectively. The rate of events leading to discontinuation of any treatment was 25.9% for pembrolizumab-axitinib and 10.1% for sunitinib, and the rate of events leading to discontinuation of both drugs in the combination was 8.2%.
Dr. Powles reported that he has a consulting or advisory role with Genentech/Roche, Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; has a nonspecified relationship with Ipsen and Bristol-Myers Squibb; receives honoraria from Roche/Genentech, Bristol-Myers Squibb, and Merck; and receives research funding from Astra-Zeneca/MedImmune and Roche/Genentech. The study was funded by Merck.
SOURCE: Powles T et al. GUCS 2019, Abstract 543.
SAN FRANCISCO – When used as first-line therapy for renal cell carcinoma (RCC), the combination of pembrolizumab and axitinib has similar safety and better efficacy than single-agent sunitinib, the current standard of care, according to findings of the KEYNOTE-426 trial that will be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.
“Axitinib is usually licensed and usually used in sunitinib-refractory disease. However, there is data for both pembrolizumab and axitinib in the frontline setting,” said lead author Thomas Powles, MBBS, MRCP, MD, of Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, and Queen Mary University of London. A phase 1b trial testing the combination showed an impressive 73% objective response rate and acceptable toxicity (Lancet Oncol. 2018;19:405-15), prompting further investigation.
The 861 patients in KEYNOTE-426, a phase 3, randomized, controlled trial, were evenly assigned to combination therapy with the immune checkpoint inhibitor pembrolizumab (Keytruda), which targets programmed death–1, plus the tyrosine kinase inhibitor axitinib (Inlyta), which targets vascular endothelial growth factor and platelet-derived growth factor, or to monotherapy with the tyrosine kinase inhibitor sunitinib (Sutent), which also targets those growth factors.
Main results reported in a presscast held before the symposium showed that, with a median follow-up of 12.8 months, pembrolizumab-axitinib reduced the risk of progression-free survival events by a relative 31% and the risk of death by a relative 47%, compared with sunitinib. The combination had a rate of grade 3-5 treatment-related adverse events similar to the rate with sunitinib alone.
“The benefit of pembrolizumab plus axitinib was seen irrespective of IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk group or PD-L1 [programmed death–ligand 1] status,” Dr. Powles noted. “Pembrolizumab and axitinib should be a standard of care in this setting, in my opinion.”
“This is a very significant trial, and it’s going to impact on patient management going forward, as it works through the regulatory process,” commented ASCO Expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, who is also deputy director and associate director of clinical research at the University of Virginia Cancer Center and a professor of medicine and urology at the University of Virginia, Charlottesville.
Study details
Patients in KEYNOTE-426 had newly diagnosed or recurrent stage IV clear cell RCC and had not received any previous systemic treatment for their advanced disease. They were randomized to pembrolizumab (200 mg intravenously every 3 weeks up to 35 cycles) plus axitinib (5 mg orally twice daily), or to sunitinib (50 mg orally once daily for first 4 weeks of each 6-week cycle).
Median overall survival was not reached in either group, but the 12-month rate was 89.9% with pembrolizumab-axitinib versus 78.3% with sunitinib, Dr. Powles reported in the presscast. The difference corresponded to a near halving of the risk of death with the combination (hazard ratio, 0.53; P less than .0001).
Median progression-free survival was 15.1 months with pembrolizumab-axitinib and 11.1 months with sunitinib. The difference corresponded to a nearly one-third reduction in the risk of events with the combination (HR, 0.69; P = .0001). “The 11.1 months is quite long for a control arm, so there’s nothing from these data to suggest that sunitinib underperformed in this trial,” he noted.
Pembrolizumab-axitinib was also associated with a higher objective response rate (59.3% vs. 35.7%; P less than .0001). The median duration of response was not reached with the former, compared with 15.2 months with the latter.
“Pembrolizumab and axitinib had a manageable safety profile,” Dr. Powles said. The rate of grade 3-5 treatment-related adverse events was 62.9% with the combination and 58.1% with sunitinib monotherapy.
The rate of events leading to death was similar at 0.9% and 1.6%, respectively. The rate of events leading to discontinuation of any treatment was 25.9% for pembrolizumab-axitinib and 10.1% for sunitinib, and the rate of events leading to discontinuation of both drugs in the combination was 8.2%.
Dr. Powles reported that he has a consulting or advisory role with Genentech/Roche, Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; has a nonspecified relationship with Ipsen and Bristol-Myers Squibb; receives honoraria from Roche/Genentech, Bristol-Myers Squibb, and Merck; and receives research funding from Astra-Zeneca/MedImmune and Roche/Genentech. The study was funded by Merck.
SOURCE: Powles T et al. GUCS 2019, Abstract 543.
REPORTING FROM GUCS 2019
Key clinical point: The combination of pembrolizumab and axitinib may become a new first-line standard of care in advanced renal cell carcinoma.
Major finding: Compared with sunitinib monotherapy, pembrolizumab and axitinib combination therapy prolonged progression-free survival (hazard ratio, 0.69; P = .0001) and overall survival (HR, 0.53; P less than .0001).
Study details: A phase 3, randomized, controlled trial among 861 patients with untreated locally advanced or metastatic renal cell carcinoma (KEYNOTE-426).
Disclosures: Dr. Powles reported that he has a consulting or advisory role with Genentech/Roche, Bristol-Myers Squibb, Merck, Novartis, and AstraZeneca; has a nonspecified relationship with Ipsen and Bristol-Myers Squibb; receives honoraria from Roche/Genentech, Bristol-Myers Squibb, and Merck; and receives research funding from AstraZeneca/MedImmune and Roche/Genentech. The study was funded by Merck.
Source: Powles T et al. GUCS 2019, Abstract 543.
Radioligand is highly active in metastatic castrate-resistant prostate cancer
SAN FRANCISCO – (LuPSMA), finds a single-center phase 2 trial to be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
“Whilst there have been major advances in the last few years with several drugs that prolong survival in these men, the disease remains fatal in a relatively short period of time, and there is an urgent need for new effective therapies,” said lead study author Michael Hofman, MBBS, professor of nuclear medicine at the Peter MacCallum Cancer Centre, Melbourne.
LuPSMA is a radiolabeled small molecule that binds with high affinity to PSMA (prostate-specific membrane antigen), enabling targeted delivery of beta radiation to lesions throughout the body. To be eligible for the trial, patients had to have PSMA-positive disease. Results among the first 30 patients treated showed good activity and acceptable toxicity (Lancet Oncol. 2018;19:825-33), leading to enrollment of an expansion cohort of 20 patients.
With a median follow-up of 23.5 months among all 50 patients, nearly two-thirds achieved a 50% or greater reduction in their PSA level, Dr. Hofman reported in a presscast held before the symposium. Median overall survival exceeded 12 months for the whole cohort and was especially good for the subset achieving that level of PSA reduction, at 18 months.
“This is a single-arm study with no control arm. So whilst my impression is that this is a life-prolonging therapy, this is not a claim that we can make yet because there is no comparator arm with an existing treatment or therapy,” he acknowledged. However, data from the literature suggest that in the absence of this novel radioligand, the patients would likely have survived only about 6-9 months.
“These results in 50 men provide further confidence to our previously published 30-patient cohort, demonstrating high response rates and low toxicity in men with mCRPC who have progressed after multiple conventional therapies,” Dr. Hofman said. The findings also “support a novel mechanism of action for this therapy compared to existing therapies.”
The favorable data have led to initiation of two randomized controlled trials: the phase 2 TheraP trial (NCT03392428) comparing LuPSMA with cabazitaxel (Jevtana), and the phase 3 VISION trial (NCT03511664), comparing LuPSMA with best standard of care. “We really need the larger trials ... to get a confident assessment on whether it improves survival and by how much,” he maintained. “But my impression, seeing these patients come into the clinic very sick and seeing them improve on the therapy, and knowing those averages [for survival without this therapy], is that these trials are likely to be positive.”
“As a clinician, I will tell you that this is a very intriguing agent, and the VISION study, which is a registration trial, is open in the U.S.,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
Study details
Of the 76 patients screened for the LuPSMA trial, 16 (21%) were ineligible because of insufficient PSMA uptake on a PSMA–FDG PET scan. “The majority of patients with this disease are suitable. Probably somewhere in the range of 20% to 30%, depending on how you measure it, may not be suitable,” Dr. Hofman said.
The 50 patients ultimately enrolled had aggressive disease, as indicated by a median PSA doubling time of 2.6 months. Most had previously received abiraterone (Zytiga), enzalutamide (Xtandi), or both (90%), as well as docetaxel (84%) or cabazitaxel (48%). “Many of these men had no further treatment options, and without this study open, they probably would have received end-of-life palliative care,” he said.
The median number of LuPSMA cycles administered was four, according to data reported in the presscast leading up to the symposium. Eight patients received fewer than four cycles because they had an exceptional response, while 10 patients did not complete all planned cycles because of disease progression.
Main results showed that PSA levels fell by at least 30% in 74% of patients, at least 50% in 64% of patients, and at least 80% in 44% of patients. Only two patients did not see any reduction. “We think this is probably a feature of our careful selection of patients with the PET scanning up front to really enrich the study for patients who are likely to benefit from the treatment,” Dr. Hofman said. The reductions in PSA were accompanied by reductions in positive lesions on PSMA–FDG PET.
For the entire cohort, median overall survival was 13.3 months. But it was significantly longer for those with versus without at least a 50% PSA decline (18.0 vs. 8.7 months; P = .001).
Fourteen patients who experienced progression on LuPSMA were given additional doses after the trial ended, as part of an off-trial expanded-access program. Fully 64% of these patients achieved a PSA reduction of at least 50%, and median overall survival in all of the retreated patients was 33 months.
Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
SOURCE: Hofman M et al. GUCS 2019, Abstract 228.
SAN FRANCISCO – (LuPSMA), finds a single-center phase 2 trial to be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
“Whilst there have been major advances in the last few years with several drugs that prolong survival in these men, the disease remains fatal in a relatively short period of time, and there is an urgent need for new effective therapies,” said lead study author Michael Hofman, MBBS, professor of nuclear medicine at the Peter MacCallum Cancer Centre, Melbourne.
LuPSMA is a radiolabeled small molecule that binds with high affinity to PSMA (prostate-specific membrane antigen), enabling targeted delivery of beta radiation to lesions throughout the body. To be eligible for the trial, patients had to have PSMA-positive disease. Results among the first 30 patients treated showed good activity and acceptable toxicity (Lancet Oncol. 2018;19:825-33), leading to enrollment of an expansion cohort of 20 patients.
With a median follow-up of 23.5 months among all 50 patients, nearly two-thirds achieved a 50% or greater reduction in their PSA level, Dr. Hofman reported in a presscast held before the symposium. Median overall survival exceeded 12 months for the whole cohort and was especially good for the subset achieving that level of PSA reduction, at 18 months.
“This is a single-arm study with no control arm. So whilst my impression is that this is a life-prolonging therapy, this is not a claim that we can make yet because there is no comparator arm with an existing treatment or therapy,” he acknowledged. However, data from the literature suggest that in the absence of this novel radioligand, the patients would likely have survived only about 6-9 months.
“These results in 50 men provide further confidence to our previously published 30-patient cohort, demonstrating high response rates and low toxicity in men with mCRPC who have progressed after multiple conventional therapies,” Dr. Hofman said. The findings also “support a novel mechanism of action for this therapy compared to existing therapies.”
The favorable data have led to initiation of two randomized controlled trials: the phase 2 TheraP trial (NCT03392428) comparing LuPSMA with cabazitaxel (Jevtana), and the phase 3 VISION trial (NCT03511664), comparing LuPSMA with best standard of care. “We really need the larger trials ... to get a confident assessment on whether it improves survival and by how much,” he maintained. “But my impression, seeing these patients come into the clinic very sick and seeing them improve on the therapy, and knowing those averages [for survival without this therapy], is that these trials are likely to be positive.”
“As a clinician, I will tell you that this is a very intriguing agent, and the VISION study, which is a registration trial, is open in the U.S.,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
Study details
Of the 76 patients screened for the LuPSMA trial, 16 (21%) were ineligible because of insufficient PSMA uptake on a PSMA–FDG PET scan. “The majority of patients with this disease are suitable. Probably somewhere in the range of 20% to 30%, depending on how you measure it, may not be suitable,” Dr. Hofman said.
The 50 patients ultimately enrolled had aggressive disease, as indicated by a median PSA doubling time of 2.6 months. Most had previously received abiraterone (Zytiga), enzalutamide (Xtandi), or both (90%), as well as docetaxel (84%) or cabazitaxel (48%). “Many of these men had no further treatment options, and without this study open, they probably would have received end-of-life palliative care,” he said.
The median number of LuPSMA cycles administered was four, according to data reported in the presscast leading up to the symposium. Eight patients received fewer than four cycles because they had an exceptional response, while 10 patients did not complete all planned cycles because of disease progression.
Main results showed that PSA levels fell by at least 30% in 74% of patients, at least 50% in 64% of patients, and at least 80% in 44% of patients. Only two patients did not see any reduction. “We think this is probably a feature of our careful selection of patients with the PET scanning up front to really enrich the study for patients who are likely to benefit from the treatment,” Dr. Hofman said. The reductions in PSA were accompanied by reductions in positive lesions on PSMA–FDG PET.
For the entire cohort, median overall survival was 13.3 months. But it was significantly longer for those with versus without at least a 50% PSA decline (18.0 vs. 8.7 months; P = .001).
Fourteen patients who experienced progression on LuPSMA were given additional doses after the trial ended, as part of an off-trial expanded-access program. Fully 64% of these patients achieved a PSA reduction of at least 50%, and median overall survival in all of the retreated patients was 33 months.
Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
SOURCE: Hofman M et al. GUCS 2019, Abstract 228.
SAN FRANCISCO – (LuPSMA), finds a single-center phase 2 trial to be reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
“Whilst there have been major advances in the last few years with several drugs that prolong survival in these men, the disease remains fatal in a relatively short period of time, and there is an urgent need for new effective therapies,” said lead study author Michael Hofman, MBBS, professor of nuclear medicine at the Peter MacCallum Cancer Centre, Melbourne.
LuPSMA is a radiolabeled small molecule that binds with high affinity to PSMA (prostate-specific membrane antigen), enabling targeted delivery of beta radiation to lesions throughout the body. To be eligible for the trial, patients had to have PSMA-positive disease. Results among the first 30 patients treated showed good activity and acceptable toxicity (Lancet Oncol. 2018;19:825-33), leading to enrollment of an expansion cohort of 20 patients.
With a median follow-up of 23.5 months among all 50 patients, nearly two-thirds achieved a 50% or greater reduction in their PSA level, Dr. Hofman reported in a presscast held before the symposium. Median overall survival exceeded 12 months for the whole cohort and was especially good for the subset achieving that level of PSA reduction, at 18 months.
“This is a single-arm study with no control arm. So whilst my impression is that this is a life-prolonging therapy, this is not a claim that we can make yet because there is no comparator arm with an existing treatment or therapy,” he acknowledged. However, data from the literature suggest that in the absence of this novel radioligand, the patients would likely have survived only about 6-9 months.
“These results in 50 men provide further confidence to our previously published 30-patient cohort, demonstrating high response rates and low toxicity in men with mCRPC who have progressed after multiple conventional therapies,” Dr. Hofman said. The findings also “support a novel mechanism of action for this therapy compared to existing therapies.”
The favorable data have led to initiation of two randomized controlled trials: the phase 2 TheraP trial (NCT03392428) comparing LuPSMA with cabazitaxel (Jevtana), and the phase 3 VISION trial (NCT03511664), comparing LuPSMA with best standard of care. “We really need the larger trials ... to get a confident assessment on whether it improves survival and by how much,” he maintained. “But my impression, seeing these patients come into the clinic very sick and seeing them improve on the therapy, and knowing those averages [for survival without this therapy], is that these trials are likely to be positive.”
“As a clinician, I will tell you that this is a very intriguing agent, and the VISION study, which is a registration trial, is open in the U.S.,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.
Study details
Of the 76 patients screened for the LuPSMA trial, 16 (21%) were ineligible because of insufficient PSMA uptake on a PSMA–FDG PET scan. “The majority of patients with this disease are suitable. Probably somewhere in the range of 20% to 30%, depending on how you measure it, may not be suitable,” Dr. Hofman said.
The 50 patients ultimately enrolled had aggressive disease, as indicated by a median PSA doubling time of 2.6 months. Most had previously received abiraterone (Zytiga), enzalutamide (Xtandi), or both (90%), as well as docetaxel (84%) or cabazitaxel (48%). “Many of these men had no further treatment options, and without this study open, they probably would have received end-of-life palliative care,” he said.
The median number of LuPSMA cycles administered was four, according to data reported in the presscast leading up to the symposium. Eight patients received fewer than four cycles because they had an exceptional response, while 10 patients did not complete all planned cycles because of disease progression.
Main results showed that PSA levels fell by at least 30% in 74% of patients, at least 50% in 64% of patients, and at least 80% in 44% of patients. Only two patients did not see any reduction. “We think this is probably a feature of our careful selection of patients with the PET scanning up front to really enrich the study for patients who are likely to benefit from the treatment,” Dr. Hofman said. The reductions in PSA were accompanied by reductions in positive lesions on PSMA–FDG PET.
For the entire cohort, median overall survival was 13.3 months. But it was significantly longer for those with versus without at least a 50% PSA decline (18.0 vs. 8.7 months; P = .001).
Fourteen patients who experienced progression on LuPSMA were given additional doses after the trial ended, as part of an off-trial expanded-access program. Fully 64% of these patients achieved a PSA reduction of at least 50%, and median overall survival in all of the retreated patients was 33 months.
Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
SOURCE: Hofman M et al. GUCS 2019, Abstract 228.
REPORTING FROM GUCS 2019
Key clinical point: Lutetium-177 PSMA-617 (LuPSMA) is highly active in PSMA-positive metastatic castrate-resistant prostate cancer.
Major finding: PSA level fell by at least 50% in 64% of men, and median overall survival was 13.3 months.
Study details: A single-center, single-arm phase 2 trial among 50 men with PSMA-positive metastatic castrate-resistant prostate cancer (LuPSMA trial).
Disclosures: Dr. Hofman disclosed that he has a consulting or advisory role with Endocyte; receives research funding (institutional) from Endocyte; and receives travel, accommodations, and/or expenses from Ipsen and Sanofi. The trial received research funding from the Peter MacCallum Cancer Centre.
Source: Hofman M et al. GUCS 2019, Abstract 228.
Watchful waiting up for low-risk prostate cancer
Conservative management for low-risk localized prostate cancer is up recently, in line with clinical practice guideline changes, while in high-risk disease, use of radical prostatectomy has increased despite a lack of new high-level evidence supporting the approach, according to researchers.
Active surveillance or watchful waiting surpassed both radical prostatectomy and radiotherapy to become the most common management strategy in low-risk disease over the 2010-2015 time period, according to their analysis of a Surveillance, Epidemiology, and End Results (SEER) database.
Meanwhile, radical prostatectomy use declined in low-risk patients, but increased in those with higher-risk disease at the expense of radiotherapy, said authors of the analysis, led by Brandon A. Mahal, MD, and Paul L. Nguyen, MD, of Dana-Farber Cancer Institute, Boston.
“Although increasing use of active surveillance or watchful waiting for low-risk disease has been supported by high-level evidence and guidelines since 2010, shifting management patterns toward more radical prostatectomy in higher-risk disease and away from radiotherapy does not coincide with any new level 1 evidence or guideline changes,” Dr. Mahal, Dr. Nguyen, and coauthors said in JAMA.
The analysis included 164,760 men with a diagnosis of localized prostate cancer between 2010 and 2015 in the SEER Prostate Active Surveillance/Watchful Waiting database. Of that group, 12.7% were managed by active surveillance or watchful waiting, while 41.5% underwent radiotherapy and 45.8% had a radical prostatectomy.
For men with low-risk disease, active surveillance or watchful waiting increased from just 14.5% in 2010 to 42.1% in 2015, investigators found. Radical prostatectomy decreased from 47.4% to 31.3% over that 5-year period, while radiotherapy likewise decreased from 38.0% to 26.6% (P less than .001 for all three trends).
By contrast, in men with high-risk disease, use of radical prostatectomy increased from 38.0% to 42.8%, while radiotherapy decreased from 60.1% to 55.0% (P less than .001 for both trends), and use of active surveillance remained low and steady at 1.9% in 2010 to 2.2% in 2015.
Intermediate-risk disease saw a significant increase in active surveillance, from 5.8% to 9.6% over the time period, with commensurate decreases in both radical prostatectomy and radiotherapy, according to the report.
While low-risk prostate cancer was traditionally managed with radical prostatectomy, national clinical practice guidelines starting in 2010 began recommending conservative management with active surveillance or watchful waiting, researchers noted in their report.
These epidemiologic data don’t provide any insights on clinical outcomes related to the management changes, investigators acknowledged. They said further study is needed to determine the “downstream effects” of increased active surveillance or watchful waiting in low-risk prostate cancer.
Dr. Mahal reported no conflicts of interest, while Dr. Nguyen provided disclosures related to Ferring, Augmenix, Bayer, Janssen, Astellas, Dendreon, Genome DX, Blue Earth Diagnostics, Cota, Nanobiotix, Janssen, and Astellas. Coauthors had disclosures relate to Janssen, Blue Earth, and the National Institutes of Health.
SOURCE: Mahal BA et al. JAMA. 2019 Feb 11. doi: 10.1001/jama.2018.19941.
Conservative management for low-risk localized prostate cancer is up recently, in line with clinical practice guideline changes, while in high-risk disease, use of radical prostatectomy has increased despite a lack of new high-level evidence supporting the approach, according to researchers.
Active surveillance or watchful waiting surpassed both radical prostatectomy and radiotherapy to become the most common management strategy in low-risk disease over the 2010-2015 time period, according to their analysis of a Surveillance, Epidemiology, and End Results (SEER) database.
Meanwhile, radical prostatectomy use declined in low-risk patients, but increased in those with higher-risk disease at the expense of radiotherapy, said authors of the analysis, led by Brandon A. Mahal, MD, and Paul L. Nguyen, MD, of Dana-Farber Cancer Institute, Boston.
“Although increasing use of active surveillance or watchful waiting for low-risk disease has been supported by high-level evidence and guidelines since 2010, shifting management patterns toward more radical prostatectomy in higher-risk disease and away from radiotherapy does not coincide with any new level 1 evidence or guideline changes,” Dr. Mahal, Dr. Nguyen, and coauthors said in JAMA.
The analysis included 164,760 men with a diagnosis of localized prostate cancer between 2010 and 2015 in the SEER Prostate Active Surveillance/Watchful Waiting database. Of that group, 12.7% were managed by active surveillance or watchful waiting, while 41.5% underwent radiotherapy and 45.8% had a radical prostatectomy.
For men with low-risk disease, active surveillance or watchful waiting increased from just 14.5% in 2010 to 42.1% in 2015, investigators found. Radical prostatectomy decreased from 47.4% to 31.3% over that 5-year period, while radiotherapy likewise decreased from 38.0% to 26.6% (P less than .001 for all three trends).
By contrast, in men with high-risk disease, use of radical prostatectomy increased from 38.0% to 42.8%, while radiotherapy decreased from 60.1% to 55.0% (P less than .001 for both trends), and use of active surveillance remained low and steady at 1.9% in 2010 to 2.2% in 2015.
Intermediate-risk disease saw a significant increase in active surveillance, from 5.8% to 9.6% over the time period, with commensurate decreases in both radical prostatectomy and radiotherapy, according to the report.
While low-risk prostate cancer was traditionally managed with radical prostatectomy, national clinical practice guidelines starting in 2010 began recommending conservative management with active surveillance or watchful waiting, researchers noted in their report.
These epidemiologic data don’t provide any insights on clinical outcomes related to the management changes, investigators acknowledged. They said further study is needed to determine the “downstream effects” of increased active surveillance or watchful waiting in low-risk prostate cancer.
Dr. Mahal reported no conflicts of interest, while Dr. Nguyen provided disclosures related to Ferring, Augmenix, Bayer, Janssen, Astellas, Dendreon, Genome DX, Blue Earth Diagnostics, Cota, Nanobiotix, Janssen, and Astellas. Coauthors had disclosures relate to Janssen, Blue Earth, and the National Institutes of Health.
SOURCE: Mahal BA et al. JAMA. 2019 Feb 11. doi: 10.1001/jama.2018.19941.
Conservative management for low-risk localized prostate cancer is up recently, in line with clinical practice guideline changes, while in high-risk disease, use of radical prostatectomy has increased despite a lack of new high-level evidence supporting the approach, according to researchers.
Active surveillance or watchful waiting surpassed both radical prostatectomy and radiotherapy to become the most common management strategy in low-risk disease over the 2010-2015 time period, according to their analysis of a Surveillance, Epidemiology, and End Results (SEER) database.
Meanwhile, radical prostatectomy use declined in low-risk patients, but increased in those with higher-risk disease at the expense of radiotherapy, said authors of the analysis, led by Brandon A. Mahal, MD, and Paul L. Nguyen, MD, of Dana-Farber Cancer Institute, Boston.
“Although increasing use of active surveillance or watchful waiting for low-risk disease has been supported by high-level evidence and guidelines since 2010, shifting management patterns toward more radical prostatectomy in higher-risk disease and away from radiotherapy does not coincide with any new level 1 evidence or guideline changes,” Dr. Mahal, Dr. Nguyen, and coauthors said in JAMA.
The analysis included 164,760 men with a diagnosis of localized prostate cancer between 2010 and 2015 in the SEER Prostate Active Surveillance/Watchful Waiting database. Of that group, 12.7% were managed by active surveillance or watchful waiting, while 41.5% underwent radiotherapy and 45.8% had a radical prostatectomy.
For men with low-risk disease, active surveillance or watchful waiting increased from just 14.5% in 2010 to 42.1% in 2015, investigators found. Radical prostatectomy decreased from 47.4% to 31.3% over that 5-year period, while radiotherapy likewise decreased from 38.0% to 26.6% (P less than .001 for all three trends).
By contrast, in men with high-risk disease, use of radical prostatectomy increased from 38.0% to 42.8%, while radiotherapy decreased from 60.1% to 55.0% (P less than .001 for both trends), and use of active surveillance remained low and steady at 1.9% in 2010 to 2.2% in 2015.
Intermediate-risk disease saw a significant increase in active surveillance, from 5.8% to 9.6% over the time period, with commensurate decreases in both radical prostatectomy and radiotherapy, according to the report.
While low-risk prostate cancer was traditionally managed with radical prostatectomy, national clinical practice guidelines starting in 2010 began recommending conservative management with active surveillance or watchful waiting, researchers noted in their report.
These epidemiologic data don’t provide any insights on clinical outcomes related to the management changes, investigators acknowledged. They said further study is needed to determine the “downstream effects” of increased active surveillance or watchful waiting in low-risk prostate cancer.
Dr. Mahal reported no conflicts of interest, while Dr. Nguyen provided disclosures related to Ferring, Augmenix, Bayer, Janssen, Astellas, Dendreon, Genome DX, Blue Earth Diagnostics, Cota, Nanobiotix, Janssen, and Astellas. Coauthors had disclosures relate to Janssen, Blue Earth, and the National Institutes of Health.
SOURCE: Mahal BA et al. JAMA. 2019 Feb 11. doi: 10.1001/jama.2018.19941.
FROM JAMA
Key clinical point: Conservative management for low-risk localized prostate cancer is up, in line with guidelines, while radical prostatectomy use has increased in high-risk disease despite a lack of new high-level evidence to support that approach.
Major finding: In men with low-risk disease, active surveillance or watchful waiting increased from 14.5% in 2010 to 42.1% in 2015, while in high-risk disease, radical prostatectomy increased from 38.0% to 42.8%
Study details: Analysis including 164,760 men with a diagnosis of localized prostate cancer between 2010 and 2015 in the SEER Prostate Active Surveillance/Watchful Waiting database.
Disclosures: Study authors reported disclosures related to Ferring, Augmenix, Bayer, Janssen, Astellas, Dendreon, Genome DX, Blue Earth Diagnostics, Cota, Nanobiotix, Janssen, Astellas, and the National Institutes of Health.
Source: Mahal BA et al. JAMA. 2019 Feb 11. doi: 10.1001/jama.2018.19941.
ADT harms likely limited to men with CV comorbidities
WASHINGTON – The cardiovascular effects of androgen deprivation therapy (ADT) for men with advanced prostate cancer are less severe than once feared, but there is evidence to suggest that men with preexisting heart failure or a history of myocardial infarction could be at excess risk for death from cardiovascular causes when they receive ADT, according to a leading prostate cancer expert.
“I think there are concerns about potential cardiovascular harm of ADT, and I think this has reduced ADT use, despite the fact that we know for most men it improves overall survival,” said Paul Nguyen, MD, a radiation oncologist at the Dana-Farber/Brigham and Women’s Cancer Center in Boston.
“In fact, when we looked recently at men with high-risk prostate cancer, this is a group where overall survival is improved by 50% if they get ADT – so it cuts the risk of death in half – but it turns out that nearly a quarter of those patients are not receiving ADT. I think that the concern about cardiovascular harm and the confusion as to where that data stands is a lot of what’s driving that right now,” he said at the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient meeting.
Randomized trial data
Dr. Nguyen noted that the evidence suggesting that ADT can increase the risk of death from cardiovascular causes came largely from three major studies:
- A 2006 study of 73,196 Medicare enrollees aged 66 or older, which found that ADT with a gonadotropin-releasing hormone (GnRH) agonist was possibly associated with increased risk of incident diabetes and cardiovascular disease (J Clin Oncol. 2006 Sep 20;24[27]:4448-56.).
- A 2007 analysis of data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CAPSURE) database on 3,262 men treated with radical prostatectomy and 1,630 men treated with radiation or cryotherapy for localized prostate cancer, which found that among those 65 and older the 5-year cumulative incidence of cardiovascular death was 5.5% for patients who received ADT, vs. 2% for those who did not (J Natl Cancer Inst. 2007 Oct 17;99[20]:1516-24).
- A 2007 study of 1,372 men in three randomized trials of radiation therapy with or without androgen suppression therapy up to 8 months in duration, which found that men 65 and older who received 6 months of androgen suppression had significantly shorter times to fatal MIs than did men who did not receive the therapy (J Clin Oncol. 2007;25[17]:2420-5).
These studies, combined with observational data, led to a 2010 consensus statement from the American Heart Association, American Cancer Society, and American Urological Association, with endorsement from the American Society for Radiation Oncology, which stated that “there may be a relation between ADT and cardiovascular events and death.”
Also in 2010, the Food and Drug Administration required new labeling on GnRH agonists warning of “increased risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke).”
Not unanimous
Two other large randomized studies (J Clin Oncol. 2008 Feb 1;26[4]:585-91 and J Clin Oncol. 2009 Jan 1;27[1]:92-9) and two retrospective studies (J Clin Oncol. 2009 Jul 20;27[21]:3452-8 and J Clin Oncol. 2011 Sep 10;29[26]3510-16) found no excess risk of cardiovascular disease from ADT, Dr. Nguyen said, prompting him and his colleagues to see whether they could get a better estimate of the actual risk.
They did so through a 2011 meta-analysis (JAMA. 2011;306[21]:2359-66) of data on 4,141 patients from eight randomized trials. They found that among patients with unfavorable-risk prostate cancer, ADT was not associated with an increased risk of cardiovascular death, but was associated with lower risks for both prostate-specific and all-cause mortality.
Subpopulations may still be at risk
Dr. Nguyen said that the principal finding of the meta-analysis, while reassuring, “doesn’t let ADT off the hook for metabolic events, diabetes which we know happens, and the possibility of nonfatal cardiac events.”
He noted that while ADT was not associated with cardiovascular disease in clinical trials, observational studies showed significantly increased risk for fatal or non-fatal MI.
One possible explanation for the difference is that observational studies included nonfatal MI, while randomized trials looked only at cardiovascular deaths. It’s also possible that ADT causes harm primarily in men with preexisting comorbidities, who are often excluded from or underrepresented in clinical trials.
Evidence from a 2009 study (JAMA. 2009 Aug 26;302[8]:866-73) showed that among men with clinical stage T1 to T3 noninvasive, nonmetastatic prostate cancer, neoadjuvant hormonal therapy with both a luteinizing hormone-releasing hormone (LHRH) agonist and a nonsteroidal antiandrogen was associated with increased risk for all-cause mortality for those with a history of coronary artery disease–induced heart failure, but not for men with either no comorbidities or only a single comorbidity such as hypertension, hypercholesterolemia, or diabetes.
Clinical considerations
The decision to treat men with prostate cancer with ADT is therefore a balancing act, Dr. Nguyen said.
“As the risk of prostate cancer death goes up, the benefit of ADT goes up. However, as the comorbidity level goes up, the potential cardiovascular harm of ADT goes up,” he said.
For patients at the extreme ends of each continuum, such as a patient with high-risk prostate cancer and no cardiovascular comorbidities or a patient with low-risk cancer but multiple CV risk factors, the decision to give or withhold ADT is relatively simple, he said.
But for patients in between, such as a man with intermediate-risk cancer and one risk factor or a man with high risk disease with multiple comorbidities, the decision is far more complex.
“This where I think the dialogue with the cardiologist really needs to come into this decision,” he said.
Evidence to support the decision comes from retrospective studies suggesting that even men with high-risk prostate cancer have poorer overall survival with ADT if they have a history of heart failure or MI.
For patients with low-risk cancer and diabetes, ADT is associated with worse overall survival, but ADT does not cause additional harm to men with intermediate- to high-risk prostate cancer who have concomitant diabetes, Dr. Nguyen said.
“My view is that ADT has not been shown to increase cardiovascular death in randomized trials, so I think that for the vast majority of patients it probably does not increase cardiovascular deaths. But I think there could very well be a vulnerable 5% of patients who might have an excess risk of cardiovascular death, and I think we have to be careful, but we still have to balance it out against their risks for prostate cancer death,” he said.
Dr. Nguyen reported consulting fees/honoraria from Astellas, Augmenix, Blue Earth Diagnostics, Cota, Dendreon, Ferring Pharmaceuticals, GenomeDx, Janssen, and Nanobiotix.
WASHINGTON – The cardiovascular effects of androgen deprivation therapy (ADT) for men with advanced prostate cancer are less severe than once feared, but there is evidence to suggest that men with preexisting heart failure or a history of myocardial infarction could be at excess risk for death from cardiovascular causes when they receive ADT, according to a leading prostate cancer expert.
“I think there are concerns about potential cardiovascular harm of ADT, and I think this has reduced ADT use, despite the fact that we know for most men it improves overall survival,” said Paul Nguyen, MD, a radiation oncologist at the Dana-Farber/Brigham and Women’s Cancer Center in Boston.
“In fact, when we looked recently at men with high-risk prostate cancer, this is a group where overall survival is improved by 50% if they get ADT – so it cuts the risk of death in half – but it turns out that nearly a quarter of those patients are not receiving ADT. I think that the concern about cardiovascular harm and the confusion as to where that data stands is a lot of what’s driving that right now,” he said at the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient meeting.
Randomized trial data
Dr. Nguyen noted that the evidence suggesting that ADT can increase the risk of death from cardiovascular causes came largely from three major studies:
- A 2006 study of 73,196 Medicare enrollees aged 66 or older, which found that ADT with a gonadotropin-releasing hormone (GnRH) agonist was possibly associated with increased risk of incident diabetes and cardiovascular disease (J Clin Oncol. 2006 Sep 20;24[27]:4448-56.).
- A 2007 analysis of data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CAPSURE) database on 3,262 men treated with radical prostatectomy and 1,630 men treated with radiation or cryotherapy for localized prostate cancer, which found that among those 65 and older the 5-year cumulative incidence of cardiovascular death was 5.5% for patients who received ADT, vs. 2% for those who did not (J Natl Cancer Inst. 2007 Oct 17;99[20]:1516-24).
- A 2007 study of 1,372 men in three randomized trials of radiation therapy with or without androgen suppression therapy up to 8 months in duration, which found that men 65 and older who received 6 months of androgen suppression had significantly shorter times to fatal MIs than did men who did not receive the therapy (J Clin Oncol. 2007;25[17]:2420-5).
These studies, combined with observational data, led to a 2010 consensus statement from the American Heart Association, American Cancer Society, and American Urological Association, with endorsement from the American Society for Radiation Oncology, which stated that “there may be a relation between ADT and cardiovascular events and death.”
Also in 2010, the Food and Drug Administration required new labeling on GnRH agonists warning of “increased risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke).”
Not unanimous
Two other large randomized studies (J Clin Oncol. 2008 Feb 1;26[4]:585-91 and J Clin Oncol. 2009 Jan 1;27[1]:92-9) and two retrospective studies (J Clin Oncol. 2009 Jul 20;27[21]:3452-8 and J Clin Oncol. 2011 Sep 10;29[26]3510-16) found no excess risk of cardiovascular disease from ADT, Dr. Nguyen said, prompting him and his colleagues to see whether they could get a better estimate of the actual risk.
They did so through a 2011 meta-analysis (JAMA. 2011;306[21]:2359-66) of data on 4,141 patients from eight randomized trials. They found that among patients with unfavorable-risk prostate cancer, ADT was not associated with an increased risk of cardiovascular death, but was associated with lower risks for both prostate-specific and all-cause mortality.
Subpopulations may still be at risk
Dr. Nguyen said that the principal finding of the meta-analysis, while reassuring, “doesn’t let ADT off the hook for metabolic events, diabetes which we know happens, and the possibility of nonfatal cardiac events.”
He noted that while ADT was not associated with cardiovascular disease in clinical trials, observational studies showed significantly increased risk for fatal or non-fatal MI.
One possible explanation for the difference is that observational studies included nonfatal MI, while randomized trials looked only at cardiovascular deaths. It’s also possible that ADT causes harm primarily in men with preexisting comorbidities, who are often excluded from or underrepresented in clinical trials.
Evidence from a 2009 study (JAMA. 2009 Aug 26;302[8]:866-73) showed that among men with clinical stage T1 to T3 noninvasive, nonmetastatic prostate cancer, neoadjuvant hormonal therapy with both a luteinizing hormone-releasing hormone (LHRH) agonist and a nonsteroidal antiandrogen was associated with increased risk for all-cause mortality for those with a history of coronary artery disease–induced heart failure, but not for men with either no comorbidities or only a single comorbidity such as hypertension, hypercholesterolemia, or diabetes.
Clinical considerations
The decision to treat men with prostate cancer with ADT is therefore a balancing act, Dr. Nguyen said.
“As the risk of prostate cancer death goes up, the benefit of ADT goes up. However, as the comorbidity level goes up, the potential cardiovascular harm of ADT goes up,” he said.
For patients at the extreme ends of each continuum, such as a patient with high-risk prostate cancer and no cardiovascular comorbidities or a patient with low-risk cancer but multiple CV risk factors, the decision to give or withhold ADT is relatively simple, he said.
But for patients in between, such as a man with intermediate-risk cancer and one risk factor or a man with high risk disease with multiple comorbidities, the decision is far more complex.
“This where I think the dialogue with the cardiologist really needs to come into this decision,” he said.
Evidence to support the decision comes from retrospective studies suggesting that even men with high-risk prostate cancer have poorer overall survival with ADT if they have a history of heart failure or MI.
For patients with low-risk cancer and diabetes, ADT is associated with worse overall survival, but ADT does not cause additional harm to men with intermediate- to high-risk prostate cancer who have concomitant diabetes, Dr. Nguyen said.
“My view is that ADT has not been shown to increase cardiovascular death in randomized trials, so I think that for the vast majority of patients it probably does not increase cardiovascular deaths. But I think there could very well be a vulnerable 5% of patients who might have an excess risk of cardiovascular death, and I think we have to be careful, but we still have to balance it out against their risks for prostate cancer death,” he said.
Dr. Nguyen reported consulting fees/honoraria from Astellas, Augmenix, Blue Earth Diagnostics, Cota, Dendreon, Ferring Pharmaceuticals, GenomeDx, Janssen, and Nanobiotix.
WASHINGTON – The cardiovascular effects of androgen deprivation therapy (ADT) for men with advanced prostate cancer are less severe than once feared, but there is evidence to suggest that men with preexisting heart failure or a history of myocardial infarction could be at excess risk for death from cardiovascular causes when they receive ADT, according to a leading prostate cancer expert.
“I think there are concerns about potential cardiovascular harm of ADT, and I think this has reduced ADT use, despite the fact that we know for most men it improves overall survival,” said Paul Nguyen, MD, a radiation oncologist at the Dana-Farber/Brigham and Women’s Cancer Center in Boston.
“In fact, when we looked recently at men with high-risk prostate cancer, this is a group where overall survival is improved by 50% if they get ADT – so it cuts the risk of death in half – but it turns out that nearly a quarter of those patients are not receiving ADT. I think that the concern about cardiovascular harm and the confusion as to where that data stands is a lot of what’s driving that right now,” he said at the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient meeting.
Randomized trial data
Dr. Nguyen noted that the evidence suggesting that ADT can increase the risk of death from cardiovascular causes came largely from three major studies:
- A 2006 study of 73,196 Medicare enrollees aged 66 or older, which found that ADT with a gonadotropin-releasing hormone (GnRH) agonist was possibly associated with increased risk of incident diabetes and cardiovascular disease (J Clin Oncol. 2006 Sep 20;24[27]:4448-56.).
- A 2007 analysis of data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CAPSURE) database on 3,262 men treated with radical prostatectomy and 1,630 men treated with radiation or cryotherapy for localized prostate cancer, which found that among those 65 and older the 5-year cumulative incidence of cardiovascular death was 5.5% for patients who received ADT, vs. 2% for those who did not (J Natl Cancer Inst. 2007 Oct 17;99[20]:1516-24).
- A 2007 study of 1,372 men in three randomized trials of radiation therapy with or without androgen suppression therapy up to 8 months in duration, which found that men 65 and older who received 6 months of androgen suppression had significantly shorter times to fatal MIs than did men who did not receive the therapy (J Clin Oncol. 2007;25[17]:2420-5).
These studies, combined with observational data, led to a 2010 consensus statement from the American Heart Association, American Cancer Society, and American Urological Association, with endorsement from the American Society for Radiation Oncology, which stated that “there may be a relation between ADT and cardiovascular events and death.”
Also in 2010, the Food and Drug Administration required new labeling on GnRH agonists warning of “increased risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke).”
Not unanimous
Two other large randomized studies (J Clin Oncol. 2008 Feb 1;26[4]:585-91 and J Clin Oncol. 2009 Jan 1;27[1]:92-9) and two retrospective studies (J Clin Oncol. 2009 Jul 20;27[21]:3452-8 and J Clin Oncol. 2011 Sep 10;29[26]3510-16) found no excess risk of cardiovascular disease from ADT, Dr. Nguyen said, prompting him and his colleagues to see whether they could get a better estimate of the actual risk.
They did so through a 2011 meta-analysis (JAMA. 2011;306[21]:2359-66) of data on 4,141 patients from eight randomized trials. They found that among patients with unfavorable-risk prostate cancer, ADT was not associated with an increased risk of cardiovascular death, but was associated with lower risks for both prostate-specific and all-cause mortality.
Subpopulations may still be at risk
Dr. Nguyen said that the principal finding of the meta-analysis, while reassuring, “doesn’t let ADT off the hook for metabolic events, diabetes which we know happens, and the possibility of nonfatal cardiac events.”
He noted that while ADT was not associated with cardiovascular disease in clinical trials, observational studies showed significantly increased risk for fatal or non-fatal MI.
One possible explanation for the difference is that observational studies included nonfatal MI, while randomized trials looked only at cardiovascular deaths. It’s also possible that ADT causes harm primarily in men with preexisting comorbidities, who are often excluded from or underrepresented in clinical trials.
Evidence from a 2009 study (JAMA. 2009 Aug 26;302[8]:866-73) showed that among men with clinical stage T1 to T3 noninvasive, nonmetastatic prostate cancer, neoadjuvant hormonal therapy with both a luteinizing hormone-releasing hormone (LHRH) agonist and a nonsteroidal antiandrogen was associated with increased risk for all-cause mortality for those with a history of coronary artery disease–induced heart failure, but not for men with either no comorbidities or only a single comorbidity such as hypertension, hypercholesterolemia, or diabetes.
Clinical considerations
The decision to treat men with prostate cancer with ADT is therefore a balancing act, Dr. Nguyen said.
“As the risk of prostate cancer death goes up, the benefit of ADT goes up. However, as the comorbidity level goes up, the potential cardiovascular harm of ADT goes up,” he said.
For patients at the extreme ends of each continuum, such as a patient with high-risk prostate cancer and no cardiovascular comorbidities or a patient with low-risk cancer but multiple CV risk factors, the decision to give or withhold ADT is relatively simple, he said.
But for patients in between, such as a man with intermediate-risk cancer and one risk factor or a man with high risk disease with multiple comorbidities, the decision is far more complex.
“This where I think the dialogue with the cardiologist really needs to come into this decision,” he said.
Evidence to support the decision comes from retrospective studies suggesting that even men with high-risk prostate cancer have poorer overall survival with ADT if they have a history of heart failure or MI.
For patients with low-risk cancer and diabetes, ADT is associated with worse overall survival, but ADT does not cause additional harm to men with intermediate- to high-risk prostate cancer who have concomitant diabetes, Dr. Nguyen said.
“My view is that ADT has not been shown to increase cardiovascular death in randomized trials, so I think that for the vast majority of patients it probably does not increase cardiovascular deaths. But I think there could very well be a vulnerable 5% of patients who might have an excess risk of cardiovascular death, and I think we have to be careful, but we still have to balance it out against their risks for prostate cancer death,” he said.
Dr. Nguyen reported consulting fees/honoraria from Astellas, Augmenix, Blue Earth Diagnostics, Cota, Dendreon, Ferring Pharmaceuticals, GenomeDx, Janssen, and Nanobiotix.
REPORTING FROM ACC CARDIO-ONCOLOGY
Key clinical point: Risk of cardiovascular death should be weighed against proven ADT benefits.
Major finding: ADT-related cardiovascular events appear limited to men with comorbid cardiovascular disease.
Study details: Review of clinical data on the cardiovascular consequences of ADT.
Disclosures: Dr. Nguyen reported consulting fees/honoraria from Astellas, Augmenix, Blue Earth Diagnostics, Cota, Dendreon, Ferring Pharmaceuticals, GenomeDx, Janssen, and Nanobiotix.
Obesity-related cancers increasing in younger adults
The incidence of obesity-related cancers such as kidney and gallbladder cancer has increased significantly in young adults over the past two decades in the United States, according to an analysis of data from 25 population-based state registries in the United States.
The incidence of 6 of the 12 obesity-related cancers increased among individuals aged 25-49 years, Hyuna Sung, PhD, of the American Cancer Society, Atlanta, and her colleagues reported Feb. 4 in the Lancet Public Health.
Among more than 14.6 million incident cases of cancer diagnosed in adults aged 25-84 years between 1995 and 2014, the greatest increase in incidence, 6.23% annually, was seen with kidney cancer among the 25- to 29-year age group. Incidence, however, also increased by at least 6.17% in those aged 30-34 years, by 5.23% in those aged 35-39 years, and by 3.88% in those aged 40-44 years.
The incidence rate for kidney cancer among individuals born around 1985 was nearly fivefold higher than in individuals born in 1950, the investigators said (Lancet Public Health. 2019 Feb 4. doi: 10.1016/S2468-2667(18)30267-6).
The analysis also showed significant increases from 1995 to 2014 in the incidence of cancer of the gallbladder among younger adults: 3.71% per year among those aged 25-29 years and 2.58% per year in those aged 30-34 years.
Similarly, the incidence of uterine corpus cancer increased in the 25- to 29-year age group by 3.34% per year and by 3.22% in the 30- to 34-year age group. The incidence of colorectal cancer increased by 2.41% among those aged 25-29 years and by 2.38% in those aged 30-34 years, Dr. Sung and her associates said.
The greatest annual increase in the incidence of multiple myeloma was seen in individuals aged 30-34 years (2.21%), but significant annual increases in incidence were seen in individuals aged 30-44 years.
For pancreatic cancer, significant annual increases in incidence were seen among individuals aged 25-29 years (4.34%) and 30-34 years (2.47%).
The study also showed increases in the same obesity-related cancers – except for colorectal cancer – among adults aged 50 years and older. The incidence of colorectal cancer actually decreased annually in older adults, while the incidence of uterine corpus cancer increased among women aged 50-69 years but decreased in those over 75 years.
Dr. Sung and her coauthors suggested that these trends may be related to the rise of obesity and overweight in the United States, noting that excess body weight could be responsible for up to 60% of all endometrial cancers, 36% of gallbladder cancers, and 33% of kidney cancers in adults aged over 30 years.
“Because most epidemiological studies have primarily focused on older populations, the effect of excess bodyweight in early life or of weight change from young adulthood on cancer risk in different stages of the life course is not well characterized,” they wrote. “In concert with excess bodyweight, obesity-related health conditions and lifestyle factors can contribute to the increasing burden of obesity-related cancers in young adults, which include diabetes, gallstones, inflammatory bowel disease, and poor diet.”
The incidences of breast cancer and gastric cardia cancer were relatively stable in all age groups over the study period, and the incidence of ovarian cancer decreased in all age groups.
Researchers looked at the incidence of 30 cancers in total, including 18 cancers not related to obesity. Here they saw increases among younger adults only in the incidence of gastric noncardiac cancer – which showed a 2.16% annual increase in incidence among those aged 30-34 years – and leukemia, where there was a 1.33% annual increase in incidence in the same age group.
But the incidence of eight cancers, including those related to smoking and infection, decreased each year among younger adults.
“Our findings expose a recent change that could serve as a warning of an increased burden of obesity-related cancers to come in older adults,” study senior author Ahmedin Jemal, PhD, of the American Cancer Society, said in a statement. “Most cancers occur in older adults, which means that as the young people in our study age, the burden of obesity-related cancer cases and deaths are likely to increase even more. On the eve of World Cancer Day, it’s timely to consider what can be done to avert the impending rise.”
The future burden of these cancers could halt or even reverse the reductions in cancer mortality achieved over the past several decades, the investigators warned.
The study was funded by the American Cancer Society and the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Sung H et al. Lancet Public Health. 2019 Feb 4 doi: 10.1016/ S2468-2667(18)30267-6.
Cancer was long thought of as a disease of aging, but the increase in incidence of some cancers in younger age groups has driven a recent reexamination of risk factors. This study’s most striking finding is the disproportionate increase in obesity-related cancer incidence among successively younger cohorts. Coupled with the rising incidence of obesity over the same period, it provides compelling evidence of a possible causal role for obesity in the increased incidence of these cancers.
Not all obesity-related cancers, however, show this pattern of age-specific increase in incidence, which could reflect the influence of other risk factors.
The hypothesis suggested by the study’s authors is plausible but needs to be tested more directly in experimental and population-based studies.
Catherine R. Marinac, PhD, is with the department of medical oncology at the Dana-Farber Cancer Institute, Boston, and Brenda M. Birmann, ScD, is with the department of medicine at Brigham and Women’s Hospital, Boston. These comments are taken from an accompanying editorial (Lancet Public Health. 2019 Feb 4. doi: 10.1016/S2468-2667(19)30017-9). No conflicts of interest were declared.
Cancer was long thought of as a disease of aging, but the increase in incidence of some cancers in younger age groups has driven a recent reexamination of risk factors. This study’s most striking finding is the disproportionate increase in obesity-related cancer incidence among successively younger cohorts. Coupled with the rising incidence of obesity over the same period, it provides compelling evidence of a possible causal role for obesity in the increased incidence of these cancers.
Not all obesity-related cancers, however, show this pattern of age-specific increase in incidence, which could reflect the influence of other risk factors.
The hypothesis suggested by the study’s authors is plausible but needs to be tested more directly in experimental and population-based studies.
Catherine R. Marinac, PhD, is with the department of medical oncology at the Dana-Farber Cancer Institute, Boston, and Brenda M. Birmann, ScD, is with the department of medicine at Brigham and Women’s Hospital, Boston. These comments are taken from an accompanying editorial (Lancet Public Health. 2019 Feb 4. doi: 10.1016/S2468-2667(19)30017-9). No conflicts of interest were declared.
Cancer was long thought of as a disease of aging, but the increase in incidence of some cancers in younger age groups has driven a recent reexamination of risk factors. This study’s most striking finding is the disproportionate increase in obesity-related cancer incidence among successively younger cohorts. Coupled with the rising incidence of obesity over the same period, it provides compelling evidence of a possible causal role for obesity in the increased incidence of these cancers.
Not all obesity-related cancers, however, show this pattern of age-specific increase in incidence, which could reflect the influence of other risk factors.
The hypothesis suggested by the study’s authors is plausible but needs to be tested more directly in experimental and population-based studies.
Catherine R. Marinac, PhD, is with the department of medical oncology at the Dana-Farber Cancer Institute, Boston, and Brenda M. Birmann, ScD, is with the department of medicine at Brigham and Women’s Hospital, Boston. These comments are taken from an accompanying editorial (Lancet Public Health. 2019 Feb 4. doi: 10.1016/S2468-2667(19)30017-9). No conflicts of interest were declared.
The incidence of obesity-related cancers such as kidney and gallbladder cancer has increased significantly in young adults over the past two decades in the United States, according to an analysis of data from 25 population-based state registries in the United States.
The incidence of 6 of the 12 obesity-related cancers increased among individuals aged 25-49 years, Hyuna Sung, PhD, of the American Cancer Society, Atlanta, and her colleagues reported Feb. 4 in the Lancet Public Health.
Among more than 14.6 million incident cases of cancer diagnosed in adults aged 25-84 years between 1995 and 2014, the greatest increase in incidence, 6.23% annually, was seen with kidney cancer among the 25- to 29-year age group. Incidence, however, also increased by at least 6.17% in those aged 30-34 years, by 5.23% in those aged 35-39 years, and by 3.88% in those aged 40-44 years.
The incidence rate for kidney cancer among individuals born around 1985 was nearly fivefold higher than in individuals born in 1950, the investigators said (Lancet Public Health. 2019 Feb 4. doi: 10.1016/S2468-2667(18)30267-6).
The analysis also showed significant increases from 1995 to 2014 in the incidence of cancer of the gallbladder among younger adults: 3.71% per year among those aged 25-29 years and 2.58% per year in those aged 30-34 years.
Similarly, the incidence of uterine corpus cancer increased in the 25- to 29-year age group by 3.34% per year and by 3.22% in the 30- to 34-year age group. The incidence of colorectal cancer increased by 2.41% among those aged 25-29 years and by 2.38% in those aged 30-34 years, Dr. Sung and her associates said.
The greatest annual increase in the incidence of multiple myeloma was seen in individuals aged 30-34 years (2.21%), but significant annual increases in incidence were seen in individuals aged 30-44 years.
For pancreatic cancer, significant annual increases in incidence were seen among individuals aged 25-29 years (4.34%) and 30-34 years (2.47%).
The study also showed increases in the same obesity-related cancers – except for colorectal cancer – among adults aged 50 years and older. The incidence of colorectal cancer actually decreased annually in older adults, while the incidence of uterine corpus cancer increased among women aged 50-69 years but decreased in those over 75 years.
Dr. Sung and her coauthors suggested that these trends may be related to the rise of obesity and overweight in the United States, noting that excess body weight could be responsible for up to 60% of all endometrial cancers, 36% of gallbladder cancers, and 33% of kidney cancers in adults aged over 30 years.
“Because most epidemiological studies have primarily focused on older populations, the effect of excess bodyweight in early life or of weight change from young adulthood on cancer risk in different stages of the life course is not well characterized,” they wrote. “In concert with excess bodyweight, obesity-related health conditions and lifestyle factors can contribute to the increasing burden of obesity-related cancers in young adults, which include diabetes, gallstones, inflammatory bowel disease, and poor diet.”
The incidences of breast cancer and gastric cardia cancer were relatively stable in all age groups over the study period, and the incidence of ovarian cancer decreased in all age groups.
Researchers looked at the incidence of 30 cancers in total, including 18 cancers not related to obesity. Here they saw increases among younger adults only in the incidence of gastric noncardiac cancer – which showed a 2.16% annual increase in incidence among those aged 30-34 years – and leukemia, where there was a 1.33% annual increase in incidence in the same age group.
But the incidence of eight cancers, including those related to smoking and infection, decreased each year among younger adults.
“Our findings expose a recent change that could serve as a warning of an increased burden of obesity-related cancers to come in older adults,” study senior author Ahmedin Jemal, PhD, of the American Cancer Society, said in a statement. “Most cancers occur in older adults, which means that as the young people in our study age, the burden of obesity-related cancer cases and deaths are likely to increase even more. On the eve of World Cancer Day, it’s timely to consider what can be done to avert the impending rise.”
The future burden of these cancers could halt or even reverse the reductions in cancer mortality achieved over the past several decades, the investigators warned.
The study was funded by the American Cancer Society and the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Sung H et al. Lancet Public Health. 2019 Feb 4 doi: 10.1016/ S2468-2667(18)30267-6.
The incidence of obesity-related cancers such as kidney and gallbladder cancer has increased significantly in young adults over the past two decades in the United States, according to an analysis of data from 25 population-based state registries in the United States.
The incidence of 6 of the 12 obesity-related cancers increased among individuals aged 25-49 years, Hyuna Sung, PhD, of the American Cancer Society, Atlanta, and her colleagues reported Feb. 4 in the Lancet Public Health.
Among more than 14.6 million incident cases of cancer diagnosed in adults aged 25-84 years between 1995 and 2014, the greatest increase in incidence, 6.23% annually, was seen with kidney cancer among the 25- to 29-year age group. Incidence, however, also increased by at least 6.17% in those aged 30-34 years, by 5.23% in those aged 35-39 years, and by 3.88% in those aged 40-44 years.
The incidence rate for kidney cancer among individuals born around 1985 was nearly fivefold higher than in individuals born in 1950, the investigators said (Lancet Public Health. 2019 Feb 4. doi: 10.1016/S2468-2667(18)30267-6).
The analysis also showed significant increases from 1995 to 2014 in the incidence of cancer of the gallbladder among younger adults: 3.71% per year among those aged 25-29 years and 2.58% per year in those aged 30-34 years.
Similarly, the incidence of uterine corpus cancer increased in the 25- to 29-year age group by 3.34% per year and by 3.22% in the 30- to 34-year age group. The incidence of colorectal cancer increased by 2.41% among those aged 25-29 years and by 2.38% in those aged 30-34 years, Dr. Sung and her associates said.
The greatest annual increase in the incidence of multiple myeloma was seen in individuals aged 30-34 years (2.21%), but significant annual increases in incidence were seen in individuals aged 30-44 years.
For pancreatic cancer, significant annual increases in incidence were seen among individuals aged 25-29 years (4.34%) and 30-34 years (2.47%).
The study also showed increases in the same obesity-related cancers – except for colorectal cancer – among adults aged 50 years and older. The incidence of colorectal cancer actually decreased annually in older adults, while the incidence of uterine corpus cancer increased among women aged 50-69 years but decreased in those over 75 years.
Dr. Sung and her coauthors suggested that these trends may be related to the rise of obesity and overweight in the United States, noting that excess body weight could be responsible for up to 60% of all endometrial cancers, 36% of gallbladder cancers, and 33% of kidney cancers in adults aged over 30 years.
“Because most epidemiological studies have primarily focused on older populations, the effect of excess bodyweight in early life or of weight change from young adulthood on cancer risk in different stages of the life course is not well characterized,” they wrote. “In concert with excess bodyweight, obesity-related health conditions and lifestyle factors can contribute to the increasing burden of obesity-related cancers in young adults, which include diabetes, gallstones, inflammatory bowel disease, and poor diet.”
The incidences of breast cancer and gastric cardia cancer were relatively stable in all age groups over the study period, and the incidence of ovarian cancer decreased in all age groups.
Researchers looked at the incidence of 30 cancers in total, including 18 cancers not related to obesity. Here they saw increases among younger adults only in the incidence of gastric noncardiac cancer – which showed a 2.16% annual increase in incidence among those aged 30-34 years – and leukemia, where there was a 1.33% annual increase in incidence in the same age group.
But the incidence of eight cancers, including those related to smoking and infection, decreased each year among younger adults.
“Our findings expose a recent change that could serve as a warning of an increased burden of obesity-related cancers to come in older adults,” study senior author Ahmedin Jemal, PhD, of the American Cancer Society, said in a statement. “Most cancers occur in older adults, which means that as the young people in our study age, the burden of obesity-related cancer cases and deaths are likely to increase even more. On the eve of World Cancer Day, it’s timely to consider what can be done to avert the impending rise.”
The future burden of these cancers could halt or even reverse the reductions in cancer mortality achieved over the past several decades, the investigators warned.
The study was funded by the American Cancer Society and the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Sung H et al. Lancet Public Health. 2019 Feb 4 doi: 10.1016/ S2468-2667(18)30267-6.
FROM THE LANCET PUBLIC HEALTH
Key clinical point: The incidence of obesity-related cancers has increased in younger adults.
Major finding: The incidence of kidney cancer has increased by more than 6% per year in younger adults since 1995.
Study details: Analysis of data from 14,672,409 cases of cancer diagnosed between 1995 and 2014.
Disclosures: The study was funded by the American Cancer Society and the National Cancer Institute. No conflicts of interest were declared.
Source: Sung H et al. Lancet Public Health. 2019 Feb 4.
The personal cancer vaccine NEO-PV-01 shows promise in metastatic cancers
WASHINGTON – according to findings from the ongoing phase 1b NT-001study of patients with metastatic melanoma, smoking-associated non–small cell lung cancer (NSCLC), and bladder cancer.
No vaccine-related serious adverse events occurred in 34 patients in a per-protocol set who were treated with the regimen, Siwen Hu-Lieskovan, MD, PhD, reported at the annual meeting of the Society for Immunotherapy of Cancer.
“We found that NEO-PV-01 in combination with nivolumab was very safe; we did not see any grade 3 to grade 4 toxicity associated with the combination,” said Dr. Hu-Lieskovan, a medical oncologist at the University of California, Los Angeles.
Most adverse events that occurred were mild and related to the local injection, she noted.
Although safety was the primary endpoint of the study, Dr. Hu-Lieskovan and her colleagues also looked at immune responses and treatment efficacy, however, with respect to translational data her presentation addressed only the findings in the melanoma and lung cancer patients.
All patients exhibited an immune response to the vaccine, with 56% of the epitopes generating CD4- and/or CD8-positive T cell responses.
“These immune responses were very durable and still could be detected 52 weeks into the treatment,” she said. Additionally, epitope spreading – increased immune response targeting nonvaccine epitopes (which is indirect evidence of vaccine-induced tumor toxicity) – was observed in 8 of 10 patients tested.
The study subjects, including 16 adults with melanoma, 11 with NSCLC, and 7 with bladder cancer, were treated with nivolumab every 2 weeks for 12 weeks prior to vaccination (while their personalized vaccine was being developed). NEO-PV-01 – which included up to 20 unique peptides plus the immunostimulant poly-ICLC – was then administered subcutaneously in five priming doses followed by two booster doses over the next 12 weeks. Of note, very few patients had programmed cell death protein 1 expression of 50% or greater, including only 13.3%, 28.6%, and 0% of the melanoma, NSCLC, and bladder cancer patients, respectively, and tumor mutation burden was consistent with published reports, she said.
As for efficacy, 11 of 16 melanoma patients (68.6%) had either a partial response (8 pre vaccination and an additional 3 post vaccination) or stable disease. One (6.3%) had a postvaccination complete response, Dr. Hu-Lieskovan said.
“[This is] much better than the historical data,” she noted, adding that 12 patients (75%) are still on the study and continuing treatment with response duration of at least 39.7 weeks.
Of the 11 NSCLC patients, 5 (45.5%) had a partial response (3 pre vaccination and 2 post vaccination), and none had a complete response. Seven (63.6%) remained on the study and were continuing treatment, and response duration was at least 30.6 weeks.
An exploratory analysis of tumor responses after vaccination showed that the majority of melanoma patients and half of the lung cancer patients had further tumor shrinkage after vaccination, and some patients were converted to responders. Most – including some with stable or progressive disease – stayed on treatment, she said.
The findings demonstrate that NEO-PV-01 is very well tolerated and associated with post vaccine responses observed after week 24.
“We saw evidence of vaccination-induced immune response specific to the injected vaccine, as well as epitope spreading, and the T cells induced by these neoantigens can traffic into the tumor and they seem to be functional,” she concluded.
Dr. Hu-Lieskovan reported receiving consulting fees and/or research support from Amgen, BMS, Genmab, Merck, and Vaccinex. She is the UCLA site principal investigator for the NT-001 study and has conducted contracted research for Astellas, F Star, Genentech, Nektar Therapeutics, Neon Therapeutics, Pfizer, Plexxikon, and Xencor.
SOURCE: Hu-Lieskovan S et al. SITC 2018, Abstract 07.
WASHINGTON – according to findings from the ongoing phase 1b NT-001study of patients with metastatic melanoma, smoking-associated non–small cell lung cancer (NSCLC), and bladder cancer.
No vaccine-related serious adverse events occurred in 34 patients in a per-protocol set who were treated with the regimen, Siwen Hu-Lieskovan, MD, PhD, reported at the annual meeting of the Society for Immunotherapy of Cancer.
“We found that NEO-PV-01 in combination with nivolumab was very safe; we did not see any grade 3 to grade 4 toxicity associated with the combination,” said Dr. Hu-Lieskovan, a medical oncologist at the University of California, Los Angeles.
Most adverse events that occurred were mild and related to the local injection, she noted.
Although safety was the primary endpoint of the study, Dr. Hu-Lieskovan and her colleagues also looked at immune responses and treatment efficacy, however, with respect to translational data her presentation addressed only the findings in the melanoma and lung cancer patients.
All patients exhibited an immune response to the vaccine, with 56% of the epitopes generating CD4- and/or CD8-positive T cell responses.
“These immune responses were very durable and still could be detected 52 weeks into the treatment,” she said. Additionally, epitope spreading – increased immune response targeting nonvaccine epitopes (which is indirect evidence of vaccine-induced tumor toxicity) – was observed in 8 of 10 patients tested.
The study subjects, including 16 adults with melanoma, 11 with NSCLC, and 7 with bladder cancer, were treated with nivolumab every 2 weeks for 12 weeks prior to vaccination (while their personalized vaccine was being developed). NEO-PV-01 – which included up to 20 unique peptides plus the immunostimulant poly-ICLC – was then administered subcutaneously in five priming doses followed by two booster doses over the next 12 weeks. Of note, very few patients had programmed cell death protein 1 expression of 50% or greater, including only 13.3%, 28.6%, and 0% of the melanoma, NSCLC, and bladder cancer patients, respectively, and tumor mutation burden was consistent with published reports, she said.
As for efficacy, 11 of 16 melanoma patients (68.6%) had either a partial response (8 pre vaccination and an additional 3 post vaccination) or stable disease. One (6.3%) had a postvaccination complete response, Dr. Hu-Lieskovan said.
“[This is] much better than the historical data,” she noted, adding that 12 patients (75%) are still on the study and continuing treatment with response duration of at least 39.7 weeks.
Of the 11 NSCLC patients, 5 (45.5%) had a partial response (3 pre vaccination and 2 post vaccination), and none had a complete response. Seven (63.6%) remained on the study and were continuing treatment, and response duration was at least 30.6 weeks.
An exploratory analysis of tumor responses after vaccination showed that the majority of melanoma patients and half of the lung cancer patients had further tumor shrinkage after vaccination, and some patients were converted to responders. Most – including some with stable or progressive disease – stayed on treatment, she said.
The findings demonstrate that NEO-PV-01 is very well tolerated and associated with post vaccine responses observed after week 24.
“We saw evidence of vaccination-induced immune response specific to the injected vaccine, as well as epitope spreading, and the T cells induced by these neoantigens can traffic into the tumor and they seem to be functional,” she concluded.
Dr. Hu-Lieskovan reported receiving consulting fees and/or research support from Amgen, BMS, Genmab, Merck, and Vaccinex. She is the UCLA site principal investigator for the NT-001 study and has conducted contracted research for Astellas, F Star, Genentech, Nektar Therapeutics, Neon Therapeutics, Pfizer, Plexxikon, and Xencor.
SOURCE: Hu-Lieskovan S et al. SITC 2018, Abstract 07.
WASHINGTON – according to findings from the ongoing phase 1b NT-001study of patients with metastatic melanoma, smoking-associated non–small cell lung cancer (NSCLC), and bladder cancer.
No vaccine-related serious adverse events occurred in 34 patients in a per-protocol set who were treated with the regimen, Siwen Hu-Lieskovan, MD, PhD, reported at the annual meeting of the Society for Immunotherapy of Cancer.
“We found that NEO-PV-01 in combination with nivolumab was very safe; we did not see any grade 3 to grade 4 toxicity associated with the combination,” said Dr. Hu-Lieskovan, a medical oncologist at the University of California, Los Angeles.
Most adverse events that occurred were mild and related to the local injection, she noted.
Although safety was the primary endpoint of the study, Dr. Hu-Lieskovan and her colleagues also looked at immune responses and treatment efficacy, however, with respect to translational data her presentation addressed only the findings in the melanoma and lung cancer patients.
All patients exhibited an immune response to the vaccine, with 56% of the epitopes generating CD4- and/or CD8-positive T cell responses.
“These immune responses were very durable and still could be detected 52 weeks into the treatment,” she said. Additionally, epitope spreading – increased immune response targeting nonvaccine epitopes (which is indirect evidence of vaccine-induced tumor toxicity) – was observed in 8 of 10 patients tested.
The study subjects, including 16 adults with melanoma, 11 with NSCLC, and 7 with bladder cancer, were treated with nivolumab every 2 weeks for 12 weeks prior to vaccination (while their personalized vaccine was being developed). NEO-PV-01 – which included up to 20 unique peptides plus the immunostimulant poly-ICLC – was then administered subcutaneously in five priming doses followed by two booster doses over the next 12 weeks. Of note, very few patients had programmed cell death protein 1 expression of 50% or greater, including only 13.3%, 28.6%, and 0% of the melanoma, NSCLC, and bladder cancer patients, respectively, and tumor mutation burden was consistent with published reports, she said.
As for efficacy, 11 of 16 melanoma patients (68.6%) had either a partial response (8 pre vaccination and an additional 3 post vaccination) or stable disease. One (6.3%) had a postvaccination complete response, Dr. Hu-Lieskovan said.
“[This is] much better than the historical data,” she noted, adding that 12 patients (75%) are still on the study and continuing treatment with response duration of at least 39.7 weeks.
Of the 11 NSCLC patients, 5 (45.5%) had a partial response (3 pre vaccination and 2 post vaccination), and none had a complete response. Seven (63.6%) remained on the study and were continuing treatment, and response duration was at least 30.6 weeks.
An exploratory analysis of tumor responses after vaccination showed that the majority of melanoma patients and half of the lung cancer patients had further tumor shrinkage after vaccination, and some patients were converted to responders. Most – including some with stable or progressive disease – stayed on treatment, she said.
The findings demonstrate that NEO-PV-01 is very well tolerated and associated with post vaccine responses observed after week 24.
“We saw evidence of vaccination-induced immune response specific to the injected vaccine, as well as epitope spreading, and the T cells induced by these neoantigens can traffic into the tumor and they seem to be functional,” she concluded.
Dr. Hu-Lieskovan reported receiving consulting fees and/or research support from Amgen, BMS, Genmab, Merck, and Vaccinex. She is the UCLA site principal investigator for the NT-001 study and has conducted contracted research for Astellas, F Star, Genentech, Nektar Therapeutics, Neon Therapeutics, Pfizer, Plexxikon, and Xencor.
SOURCE: Hu-Lieskovan S et al. SITC 2018, Abstract 07.
REPORTING FROM SITC 2018
Key clinical point: The NEO-PV-01 personalized cancer vaccine shows good tolerability and safety and appears to have clinical efficacy.
Major finding: There were no vaccine-related serious adverse events, and all patients exhibited an immune response to the vaccine, with 56% of the epitopes generating CD4- and/or CD8-positive T-cell responses.
Study details: A study of the NEO-PV-01 personalized cancer vaccine in 34 patients.
Disclosures: Dr. Hu-Lieskovan reported receiving consulting fees and/or research support from Amgen, BMS, Genmab, Merck, and Vaccinex. She is the UCLA site principal investigator for the NT-001 study and has conducted contracted research for Astellas, F Star, Genentech, Nektar Therapeutics, Neon Therapeutics, Pfizer, Plexxikon, and Xencor.
Source: Hu-Lieskovan S et al. SITC 2018, Abstract 07.
No gains from docetaxel in localized prostate cancer
The addition of docetaxel to androgen deprivation therapy in patients with localized, high-risk prostate cancer does not appear to impact progression-free survival rates, a study has found.
In JAMA Oncology, researchers reported the results of an open-label, phase 3, randomized superiority trial comparing androgen deprivation therapy (ADT) plus docetaxel with androgen therapy alone in 254 patients who had received primary local therapy for prostate cancer but showed significant risk factors for metastatic disease.
These risk factors included positive surgical margins, a Gleason score of 8 or above, prostate-specific antigen (PSA) velocity greater than 0.75 ng/mL per year, PSA doubling time of 6 months or less, and time to PSA recurrence of 12 months or less.
Overall, 63.2% of patients in the ADT plus docetaxel group and 64.8% of the ADT-only group experienced PSA progression, defined as a 50% or more relative increase in PSA levels above the nadir. After a median follow-up of 30 months, the median PSA progression-free survival (PFS) was 20.3 months in the combined therapy arm and 19.3 months in the monotherapy arm (hazard ratio, 0.85; P = .31).
“It follows that docetaxel may not be as suitable in a high-risk setting as in a metastatic setting,” wrote Stéphane Oudard, MD, PhD, from the department of medical oncology at Georges Pompidou Hospital in Paris, and his coauthors.
However individuals in the combined therapy arm showed a significantly higher complete PSA response rate, compared with those in the ADT-only group (72.8% vs. 64.8%).
In subgroup analysis, based on the various risk factors for progression to metastatic disease, the combined therapy approach was always better than the monotherapy in PSA PFS, but never achieved statistical significance. The authors noted a 15% improvement in time to PSA progression with combined therapy.
Researchers followed the group for a median of 10.5 years, during which time they saw a similar median time to radiologic progression in both arms (8.9 years for ADT plus docetaxel and 9 years for ADT alone; HR, 1.03; P = 0.88).
There was also no significant difference in all-cause mortality between the two groups.
The authors acknowledged that the clinical relevance of their chosen end point of PSA PFS was likely to be disputed, as some preferred to use endpoints such as prostate cancer mortality, metastasis-free survival, or time to metastasis.
“However, PSA PFS was an appropriate choice within our study setting and time frame because PFS depends on any subsequent PSA relapse management [e.g., reintroduction of intermittent or continuous ADT, administration of new drugs] and regular PSA sampling for landmark analyses would have been more difficult to obtain as main endpoint.”
The study was supported by Sanofi, Ipsen, and the Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie. Four authors reported receiving funding from private industry, including the study sponsors, either during the conduct of the study or outside it.
SOURCE: Oudard S et al. JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6607.
Early use of docetaxel in addition to adjuvant androgen deprivation therapy had been hypothesized as a possible path to a cure for prostate cancer – just as early adjuvant chemotherapy has shown benefits in breast cancer – but this optimism has been shown by this and other studies to be unfounded.
This study also suggests that the androgen environment is more important than disease burden when selecting adjuvant therapy – whether the disease is localized or metastatic. There may still be some patients who will benefit from adjuvant taxane therapy, but these patients are yet to be identified.
Nicholas J. Vogelzang, MD, is from the Comprehensive Cancer Centers of Nevada in Las Vegas. These comments are taken from an accompanying editorial (JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6604). Dr Vogelzang reported receiving personal fees, legal consulting roles, and stock options in the pharmaceutical industry.
Early use of docetaxel in addition to adjuvant androgen deprivation therapy had been hypothesized as a possible path to a cure for prostate cancer – just as early adjuvant chemotherapy has shown benefits in breast cancer – but this optimism has been shown by this and other studies to be unfounded.
This study also suggests that the androgen environment is more important than disease burden when selecting adjuvant therapy – whether the disease is localized or metastatic. There may still be some patients who will benefit from adjuvant taxane therapy, but these patients are yet to be identified.
Nicholas J. Vogelzang, MD, is from the Comprehensive Cancer Centers of Nevada in Las Vegas. These comments are taken from an accompanying editorial (JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6604). Dr Vogelzang reported receiving personal fees, legal consulting roles, and stock options in the pharmaceutical industry.
Early use of docetaxel in addition to adjuvant androgen deprivation therapy had been hypothesized as a possible path to a cure for prostate cancer – just as early adjuvant chemotherapy has shown benefits in breast cancer – but this optimism has been shown by this and other studies to be unfounded.
This study also suggests that the androgen environment is more important than disease burden when selecting adjuvant therapy – whether the disease is localized or metastatic. There may still be some patients who will benefit from adjuvant taxane therapy, but these patients are yet to be identified.
Nicholas J. Vogelzang, MD, is from the Comprehensive Cancer Centers of Nevada in Las Vegas. These comments are taken from an accompanying editorial (JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6604). Dr Vogelzang reported receiving personal fees, legal consulting roles, and stock options in the pharmaceutical industry.
The addition of docetaxel to androgen deprivation therapy in patients with localized, high-risk prostate cancer does not appear to impact progression-free survival rates, a study has found.
In JAMA Oncology, researchers reported the results of an open-label, phase 3, randomized superiority trial comparing androgen deprivation therapy (ADT) plus docetaxel with androgen therapy alone in 254 patients who had received primary local therapy for prostate cancer but showed significant risk factors for metastatic disease.
These risk factors included positive surgical margins, a Gleason score of 8 or above, prostate-specific antigen (PSA) velocity greater than 0.75 ng/mL per year, PSA doubling time of 6 months or less, and time to PSA recurrence of 12 months or less.
Overall, 63.2% of patients in the ADT plus docetaxel group and 64.8% of the ADT-only group experienced PSA progression, defined as a 50% or more relative increase in PSA levels above the nadir. After a median follow-up of 30 months, the median PSA progression-free survival (PFS) was 20.3 months in the combined therapy arm and 19.3 months in the monotherapy arm (hazard ratio, 0.85; P = .31).
“It follows that docetaxel may not be as suitable in a high-risk setting as in a metastatic setting,” wrote Stéphane Oudard, MD, PhD, from the department of medical oncology at Georges Pompidou Hospital in Paris, and his coauthors.
However individuals in the combined therapy arm showed a significantly higher complete PSA response rate, compared with those in the ADT-only group (72.8% vs. 64.8%).
In subgroup analysis, based on the various risk factors for progression to metastatic disease, the combined therapy approach was always better than the monotherapy in PSA PFS, but never achieved statistical significance. The authors noted a 15% improvement in time to PSA progression with combined therapy.
Researchers followed the group for a median of 10.5 years, during which time they saw a similar median time to radiologic progression in both arms (8.9 years for ADT plus docetaxel and 9 years for ADT alone; HR, 1.03; P = 0.88).
There was also no significant difference in all-cause mortality between the two groups.
The authors acknowledged that the clinical relevance of their chosen end point of PSA PFS was likely to be disputed, as some preferred to use endpoints such as prostate cancer mortality, metastasis-free survival, or time to metastasis.
“However, PSA PFS was an appropriate choice within our study setting and time frame because PFS depends on any subsequent PSA relapse management [e.g., reintroduction of intermittent or continuous ADT, administration of new drugs] and regular PSA sampling for landmark analyses would have been more difficult to obtain as main endpoint.”
The study was supported by Sanofi, Ipsen, and the Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie. Four authors reported receiving funding from private industry, including the study sponsors, either during the conduct of the study or outside it.
SOURCE: Oudard S et al. JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6607.
The addition of docetaxel to androgen deprivation therapy in patients with localized, high-risk prostate cancer does not appear to impact progression-free survival rates, a study has found.
In JAMA Oncology, researchers reported the results of an open-label, phase 3, randomized superiority trial comparing androgen deprivation therapy (ADT) plus docetaxel with androgen therapy alone in 254 patients who had received primary local therapy for prostate cancer but showed significant risk factors for metastatic disease.
These risk factors included positive surgical margins, a Gleason score of 8 or above, prostate-specific antigen (PSA) velocity greater than 0.75 ng/mL per year, PSA doubling time of 6 months or less, and time to PSA recurrence of 12 months or less.
Overall, 63.2% of patients in the ADT plus docetaxel group and 64.8% of the ADT-only group experienced PSA progression, defined as a 50% or more relative increase in PSA levels above the nadir. After a median follow-up of 30 months, the median PSA progression-free survival (PFS) was 20.3 months in the combined therapy arm and 19.3 months in the monotherapy arm (hazard ratio, 0.85; P = .31).
“It follows that docetaxel may not be as suitable in a high-risk setting as in a metastatic setting,” wrote Stéphane Oudard, MD, PhD, from the department of medical oncology at Georges Pompidou Hospital in Paris, and his coauthors.
However individuals in the combined therapy arm showed a significantly higher complete PSA response rate, compared with those in the ADT-only group (72.8% vs. 64.8%).
In subgroup analysis, based on the various risk factors for progression to metastatic disease, the combined therapy approach was always better than the monotherapy in PSA PFS, but never achieved statistical significance. The authors noted a 15% improvement in time to PSA progression with combined therapy.
Researchers followed the group for a median of 10.5 years, during which time they saw a similar median time to radiologic progression in both arms (8.9 years for ADT plus docetaxel and 9 years for ADT alone; HR, 1.03; P = 0.88).
There was also no significant difference in all-cause mortality between the two groups.
The authors acknowledged that the clinical relevance of their chosen end point of PSA PFS was likely to be disputed, as some preferred to use endpoints such as prostate cancer mortality, metastasis-free survival, or time to metastasis.
“However, PSA PFS was an appropriate choice within our study setting and time frame because PFS depends on any subsequent PSA relapse management [e.g., reintroduction of intermittent or continuous ADT, administration of new drugs] and regular PSA sampling for landmark analyses would have been more difficult to obtain as main endpoint.”
The study was supported by Sanofi, Ipsen, and the Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie. Four authors reported receiving funding from private industry, including the study sponsors, either during the conduct of the study or outside it.
SOURCE: Oudard S et al. JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6607.
FROM JAMA ONCOLOGY
Key clinical point: Docetaxel does not improve survival in localized, high-risk prostate cancer.
Major finding: Survival rates were similar in patients with localized, high-risk prostate cancer treated with or without docetaxel.
Study details: An open-label, phase 3, randomized superiority trial in 254 patients with prostate cancer.
Disclosures: The study was supported by Sanofi, Ipsen, and the Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie. Four authors reported receiving funding from private industry, including the study sponsors, either during the conduct of the study or outside it.
Source: Oudard S et al. JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6607.
Poor-prognosis cancers linked to highest suicide risk in first year
Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.
Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.
That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.
“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.
Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.
The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.
Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.
Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.
The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.
Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.
Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.
Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.
“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.
Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).
SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.
Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.
Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.
That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.
“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.
Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.
The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.
Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.
Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.
The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.
Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.
Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.
Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.
“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.
Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).
SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.
Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.
Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.
That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.
“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.
Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.
The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.
Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.
Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.
The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.
Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.
Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.
Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.
“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.
Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).
SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.
FROM CANCER
Key clinical point: A cancer diagnosis significantly increases risk of suicide in comparison to the general population, particularly for poorer-prognosis cancers.
Major finding: The observed-to-expected mortality ratio was substantially higher for pancreatic cancer (8.01), and lung cancer (6.05), but not significantly increased for breast (1.23) and prostate (0.99).
Study details: A retrospective population-based study of 4,671,989 cancer patients.
Disclosures: The authors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service.
Source: Saad AM et al. Cancer. 2019 Jan 7. doi: 10.1002/cncr.31876.