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Cabozantinib used as first-line therapy prolongs PFS for metastatic RCC
COPENHAGEN – For patients with previously untreated intermediate- or poor-risk renal cell carcinoma (RCC), cabozantanib offers a progression-free survival benefit better than that seen with sunitinib, the current standard of care, reported investigators in the phase II CABOSUN trial.
After a median follow-up of 20.8 months, progression-free survival (PFS) for patients assigned to cabozantinib (Canbometyx) the primary endpoint, was a median 8.2 months, compared with 5.6 months for patients assigned to sunitinib, reported Toni K. Choueiri, MD, from the Dana-Farber Cancer Institute in Boston.
“Cabozantinib represents a potential new treatment option for patients with untreated renal cell carcinoma,” Dr. Choueiri said at the European Society for Medical Oncology (ESMO) congress.
Sunitinib (Sutent), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) is the standard first-line therapy for patients who present with metastatic RCC. But patients with intermediate- or poor-risk metastatic RCC have shorter survival on sunitinib compared with patients with favorable-risk disease, Dr. Choueiri noted.
Resistance to VEGFR inhibitors in clear-cell RCC can arise through inactivation of the Von Hippel-Lindau (VHL) gene, which leads to upregulation of MET, AXL, and VEGF receptors.
Increased expression of MET and AXL has been associated with resistant to VEGFR inhibitors and poor clinical outcomes, he explained.
Cabozantib is an oral small-molecular inhibitor of multiple tyrosine kinases, including VEGF receptors, MET, and AXL. It is approved in the United States and Europe for use in the second-line setting following prior therapy with a VEGFR inhibitor.
Trial details
In the CABOSUN trial, 157 treatment-naive patients with clear-cell RCC with measurable disease, Eastern Cooperative Oncology Group performance status 0-2 and intermediate- or poor-risk disease according to International Metastatic Renal Cell Carcinoma Database (IMDC) criteria were randomly assigned to receive either oral cabaozantinib 60 mg daily for 6 week cycles, or oral sunitinib 50 mg daily on a standard schedule of 4 weeks on and 2 weeks off.
Tumors were assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) every other cycle, and treatment was continued to the point of disease progression or intolerable toxicity.
A total of 79 patients were assigned to cabozantinib, 78 received it, and 13 were still on the drug at the time of the data cutoff. In all, 78 patients were assigned to sunitinib, 72 received it, and 2 were continuing treatment at last follow-up. The efficacy analysis was by intention-to-treat, and the safety analysis as-treated.
As noted, median PFS was 8.2.months for cabozantinib vs. 5.6 months for sunitinib, The hazard ratio for cabozatinib was 0.69 (P = .012). A subgroup analysis showed a trend favoring cabozantinib in each risk group, but this was not significant except among patients with bone metastases (HR, 0.51; 95% confidence interval, 0.29-0.90).
The overall response rate among patients on cabozantib was 46%, compared with 18% for sunitinib. Complete responses were seen in one patient in each group, partial responses in 35 and 13, respectively, stable disease in 26 and 28, and disease progression in 14 and 20 (data on 3 and 16 patients were not evaluable).
The overall survival analysis hinted at a benefit for cabozantinib (HR, 0.80), but this was not statistically significant.
All cause grade 3 or 4 adverse events occurred in 65% of patients in the cabozantinib arm and 68% in the sunitinib arm. Events occurring more frequently with cabozantinib were hypertension (28% vs. 22%), elevated alanine aminotranseferase (5% vs. 0%), anorexia (5% vs. 0%), palmar-plantar erythrodysethesia (8% vs. 4%), and weight loss (4% vs. 0%).
There were 3 deaths possibly, probably, or definitely related to treatment among 3 patients on cabozantinib and 2 on sunitinib.
Favorable data, but wait and see
“I think cabozantinib is superior to sunitinib in poor and intermediate risk metastatic renal cell cancer,” said invited discussant Bernard Escudier, MD, from the Gustave Roussy Cancer Center in Paris.
“Cabozantinib is a potent VEGF inhibitor and is probably also active in good risk patients, although we need to see the data in these patients,” he said.
He added that a phase 3 study is warranted to confirm these conclusions, and that he will likely wait until those data are available before moving patients to cabozantinib in the first line.
The trial was supported by the National Cancer Institute. Dr. Choueiri disclosed advising and institutional research funding from Exelixis, maker of cabozantinib, and Pfizer, maker of sunitinib. Dr. Escudier disclosed receiving honoraria from each company.
op@frontlinemedcom.com
COPENHAGEN – For patients with previously untreated intermediate- or poor-risk renal cell carcinoma (RCC), cabozantanib offers a progression-free survival benefit better than that seen with sunitinib, the current standard of care, reported investigators in the phase II CABOSUN trial.
After a median follow-up of 20.8 months, progression-free survival (PFS) for patients assigned to cabozantinib (Canbometyx) the primary endpoint, was a median 8.2 months, compared with 5.6 months for patients assigned to sunitinib, reported Toni K. Choueiri, MD, from the Dana-Farber Cancer Institute in Boston.
“Cabozantinib represents a potential new treatment option for patients with untreated renal cell carcinoma,” Dr. Choueiri said at the European Society for Medical Oncology (ESMO) congress.
Sunitinib (Sutent), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) is the standard first-line therapy for patients who present with metastatic RCC. But patients with intermediate- or poor-risk metastatic RCC have shorter survival on sunitinib compared with patients with favorable-risk disease, Dr. Choueiri noted.
Resistance to VEGFR inhibitors in clear-cell RCC can arise through inactivation of the Von Hippel-Lindau (VHL) gene, which leads to upregulation of MET, AXL, and VEGF receptors.
Increased expression of MET and AXL has been associated with resistant to VEGFR inhibitors and poor clinical outcomes, he explained.
Cabozantib is an oral small-molecular inhibitor of multiple tyrosine kinases, including VEGF receptors, MET, and AXL. It is approved in the United States and Europe for use in the second-line setting following prior therapy with a VEGFR inhibitor.
Trial details
In the CABOSUN trial, 157 treatment-naive patients with clear-cell RCC with measurable disease, Eastern Cooperative Oncology Group performance status 0-2 and intermediate- or poor-risk disease according to International Metastatic Renal Cell Carcinoma Database (IMDC) criteria were randomly assigned to receive either oral cabaozantinib 60 mg daily for 6 week cycles, or oral sunitinib 50 mg daily on a standard schedule of 4 weeks on and 2 weeks off.
Tumors were assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) every other cycle, and treatment was continued to the point of disease progression or intolerable toxicity.
A total of 79 patients were assigned to cabozantinib, 78 received it, and 13 were still on the drug at the time of the data cutoff. In all, 78 patients were assigned to sunitinib, 72 received it, and 2 were continuing treatment at last follow-up. The efficacy analysis was by intention-to-treat, and the safety analysis as-treated.
As noted, median PFS was 8.2.months for cabozantinib vs. 5.6 months for sunitinib, The hazard ratio for cabozatinib was 0.69 (P = .012). A subgroup analysis showed a trend favoring cabozantinib in each risk group, but this was not significant except among patients with bone metastases (HR, 0.51; 95% confidence interval, 0.29-0.90).
The overall response rate among patients on cabozantib was 46%, compared with 18% for sunitinib. Complete responses were seen in one patient in each group, partial responses in 35 and 13, respectively, stable disease in 26 and 28, and disease progression in 14 and 20 (data on 3 and 16 patients were not evaluable).
The overall survival analysis hinted at a benefit for cabozantinib (HR, 0.80), but this was not statistically significant.
All cause grade 3 or 4 adverse events occurred in 65% of patients in the cabozantinib arm and 68% in the sunitinib arm. Events occurring more frequently with cabozantinib were hypertension (28% vs. 22%), elevated alanine aminotranseferase (5% vs. 0%), anorexia (5% vs. 0%), palmar-plantar erythrodysethesia (8% vs. 4%), and weight loss (4% vs. 0%).
There were 3 deaths possibly, probably, or definitely related to treatment among 3 patients on cabozantinib and 2 on sunitinib.
Favorable data, but wait and see
“I think cabozantinib is superior to sunitinib in poor and intermediate risk metastatic renal cell cancer,” said invited discussant Bernard Escudier, MD, from the Gustave Roussy Cancer Center in Paris.
“Cabozantinib is a potent VEGF inhibitor and is probably also active in good risk patients, although we need to see the data in these patients,” he said.
He added that a phase 3 study is warranted to confirm these conclusions, and that he will likely wait until those data are available before moving patients to cabozantinib in the first line.
The trial was supported by the National Cancer Institute. Dr. Choueiri disclosed advising and institutional research funding from Exelixis, maker of cabozantinib, and Pfizer, maker of sunitinib. Dr. Escudier disclosed receiving honoraria from each company.
op@frontlinemedcom.com
COPENHAGEN – For patients with previously untreated intermediate- or poor-risk renal cell carcinoma (RCC), cabozantanib offers a progression-free survival benefit better than that seen with sunitinib, the current standard of care, reported investigators in the phase II CABOSUN trial.
After a median follow-up of 20.8 months, progression-free survival (PFS) for patients assigned to cabozantinib (Canbometyx) the primary endpoint, was a median 8.2 months, compared with 5.6 months for patients assigned to sunitinib, reported Toni K. Choueiri, MD, from the Dana-Farber Cancer Institute in Boston.
“Cabozantinib represents a potential new treatment option for patients with untreated renal cell carcinoma,” Dr. Choueiri said at the European Society for Medical Oncology (ESMO) congress.
Sunitinib (Sutent), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) is the standard first-line therapy for patients who present with metastatic RCC. But patients with intermediate- or poor-risk metastatic RCC have shorter survival on sunitinib compared with patients with favorable-risk disease, Dr. Choueiri noted.
Resistance to VEGFR inhibitors in clear-cell RCC can arise through inactivation of the Von Hippel-Lindau (VHL) gene, which leads to upregulation of MET, AXL, and VEGF receptors.
Increased expression of MET and AXL has been associated with resistant to VEGFR inhibitors and poor clinical outcomes, he explained.
Cabozantib is an oral small-molecular inhibitor of multiple tyrosine kinases, including VEGF receptors, MET, and AXL. It is approved in the United States and Europe for use in the second-line setting following prior therapy with a VEGFR inhibitor.
Trial details
In the CABOSUN trial, 157 treatment-naive patients with clear-cell RCC with measurable disease, Eastern Cooperative Oncology Group performance status 0-2 and intermediate- or poor-risk disease according to International Metastatic Renal Cell Carcinoma Database (IMDC) criteria were randomly assigned to receive either oral cabaozantinib 60 mg daily for 6 week cycles, or oral sunitinib 50 mg daily on a standard schedule of 4 weeks on and 2 weeks off.
Tumors were assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) every other cycle, and treatment was continued to the point of disease progression or intolerable toxicity.
A total of 79 patients were assigned to cabozantinib, 78 received it, and 13 were still on the drug at the time of the data cutoff. In all, 78 patients were assigned to sunitinib, 72 received it, and 2 were continuing treatment at last follow-up. The efficacy analysis was by intention-to-treat, and the safety analysis as-treated.
As noted, median PFS was 8.2.months for cabozantinib vs. 5.6 months for sunitinib, The hazard ratio for cabozatinib was 0.69 (P = .012). A subgroup analysis showed a trend favoring cabozantinib in each risk group, but this was not significant except among patients with bone metastases (HR, 0.51; 95% confidence interval, 0.29-0.90).
The overall response rate among patients on cabozantib was 46%, compared with 18% for sunitinib. Complete responses were seen in one patient in each group, partial responses in 35 and 13, respectively, stable disease in 26 and 28, and disease progression in 14 and 20 (data on 3 and 16 patients were not evaluable).
The overall survival analysis hinted at a benefit for cabozantinib (HR, 0.80), but this was not statistically significant.
All cause grade 3 or 4 adverse events occurred in 65% of patients in the cabozantinib arm and 68% in the sunitinib arm. Events occurring more frequently with cabozantinib were hypertension (28% vs. 22%), elevated alanine aminotranseferase (5% vs. 0%), anorexia (5% vs. 0%), palmar-plantar erythrodysethesia (8% vs. 4%), and weight loss (4% vs. 0%).
There were 3 deaths possibly, probably, or definitely related to treatment among 3 patients on cabozantinib and 2 on sunitinib.
Favorable data, but wait and see
“I think cabozantinib is superior to sunitinib in poor and intermediate risk metastatic renal cell cancer,” said invited discussant Bernard Escudier, MD, from the Gustave Roussy Cancer Center in Paris.
“Cabozantinib is a potent VEGF inhibitor and is probably also active in good risk patients, although we need to see the data in these patients,” he said.
He added that a phase 3 study is warranted to confirm these conclusions, and that he will likely wait until those data are available before moving patients to cabozantinib in the first line.
The trial was supported by the National Cancer Institute. Dr. Choueiri disclosed advising and institutional research funding from Exelixis, maker of cabozantinib, and Pfizer, maker of sunitinib. Dr. Escudier disclosed receiving honoraria from each company.
op@frontlinemedcom.com
AT ESMO 2016
Key clinical point:
Major finding: Median progression-free survival for patients assigned to cabozantinib was 8.2 months, compared with 5.6 months for patients assigned to sunitinib,
Data source: Randomized phase II trial involving 157 patients with previously untreated metastatic RCC.
Disclosures: The trial was supported by the National Cancer Institute. Dr. Choueiri disclosed advising and institutional research funding from Exelixis, maker of cabozantinib, and Pfizer, maker of sunitinib. Dr. Escudier disclosed receiving honoraria from each company.
Adjuvant sunitinib offers DFS edge in high-risk RCC
COPENHAGEN – In patients with high-risk locoregional clear cell renal cell (RCC) carcinoma, adjuvant therapy with sunitinib significantly prolonged disease-free survival, compared with placebo, reported investigators in a randomized, phase III trial.
Among 615 patients with clear cell RCC at high risk for recurrence following nephrectomy, the median duration of disease-free survival (DFS) by blinded central review was 6.8 years for patients treated with sunitinib (Sutent) for 1 year, compared with 5.6 years for patients assigned to placebo, reported Alain Ravaud, MD, PhD from Hôpital Saint André in Bordeaux, France.
“These results represent a major step forward in the clinical management of clear cell renal cell carcinoma,” he said at the European Society for Medical Oncology Congress.
The study was published simultaneously online in the New England Journal of Medicine.
Approximately 16% of all patients with RCC have locoregional (stage III) disease, which is associated with a 5-year survival rate of 53%. Up to 40% of patients with locoregional disease will have a relapse with metastases after nephrectomy, indicating a need for effective adjuvant therapy to reduce the risk of relapse in this population, Dr. Ravaud said.
However, to date, adjuvant therapy with either cytokines, hormones, immunotherapy, or radiotherapy has not been successful at preventing relapse, and the ASSURE trial, comparing sunitinib and sorafenib (Nexavar) with placebo showed that neither of the tyrosine kinase inhibitors (TKIs) improved survival, and each necessitated discontinuations due to toxicity, despite dose reductions, Dr. Ravaud noted.
The trial reported here, S-TRAC (Sunitinib as Adjuvant Treatment for Patients at High Risk of Recurrence of Renal Cell Carcinoma Following Nephrectomy), had different results, however.
A total of 615 patients with high-risk RCC were enrolled. High-risk disease was defined as stage T3, NO or Nx, M0, any Furhman grade and any Eastern Cooperative Oncology Group (ECOG) performance status; T4, N0 or NX, M0, any Fuhrman/ECOG status; or any T, N1-N2, M0, any Fuhrman/ECOG status.
Patients were stratified by risk groups, ECOG status, and country, then randomized to receive either sunitinib 50 mg daily or placebo on a 4 weeks–on, 2 weeks–off schedule for 1 year or until recurrence, unacceptable toxicity, or withdrawal of consent.
Central Reviewers Yes, Investigators No
As noted before, the duration of median DFS, the primary endpoint, was 14 months longer with sunitinib, translating into a hazard ratio (HR) of 0.76 (P = .03). This determination of DFS was performed by central reviewers blinded to treatment type.
However, DFS rates by investigators review, while numerically different between trial arms (6.5 years for sunitinib vs. 4.5 years in the placebo group), were not statistically significant (HR, 0.81, P = .08).
Overall survival data were not mature at the time of the data cutoff, with the median not reached in either group.
Treatment-emergent adverse events were seen in 99.7% of the patients in the sunitinib group and in 88.5% of controls. Investigators attributed adverse events to treatment in 98.4% of patients in the sunitinib arm and 75.7% of those in the placebo arm.
The most common adverse events in the sunitinib group were diarrhea, palmar-plantar erythrodysesthesia, hypertension, fatigue, and nausea.
Grade 3 or higher adverse events were reported in 194 patients (63.4%) in the sunitinib group and in 66 (21.7%) in the placebo group.
Interestingly, there were fewer dose reductions in the sunitinib group (34.3% vs. 46.4%) and fewer dose interruptions (2.0% vs. 13.2%), although more patients on sunitinib discontinued because of adverse events (28.1% vs. 5.6%).
The most common cause of death in each group was RCC, which accounted for 47 of 62 deaths (75.8%) in the sunitinib arm and 47 of 64 (73.4%) in the placebo arm. No death was attributed to treatment-associated toxicities.
Patients on sunitinib also had generally lower scores on quality of life scales, but the between-group differences did not reach the prespecified minimally important difference of 10 patients except for the domains of diarrhea and loss of appetite.
But having said that, he noted that, in S-TRAC as in ASSURE, the study was negative going by investigator rather than central review, and that the positive HR for central review in S-TRAC was near the significance boundary.
Overall, the quality of evidence supporting sunitinib in the adjuvant setting is weak, with benefits barely outweighing harms, and that the cost of the therapy, in light of the above, is high, Dr. Bex said.
He added that he would need to see mature overall survival data from S-TRAC and ASSURE, further results from other ongoing trials with sunitinib, and a positive meta-analysis of studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors in the adjuvant setting before he would change his mind on the use of sunitinib and related agents.
The trial was supported by Pfizer. Dr. Ravaud and Dr. Bex disclosed consulting and research grants from Pfizer and other companies.
COPENHAGEN – In patients with high-risk locoregional clear cell renal cell (RCC) carcinoma, adjuvant therapy with sunitinib significantly prolonged disease-free survival, compared with placebo, reported investigators in a randomized, phase III trial.
Among 615 patients with clear cell RCC at high risk for recurrence following nephrectomy, the median duration of disease-free survival (DFS) by blinded central review was 6.8 years for patients treated with sunitinib (Sutent) for 1 year, compared with 5.6 years for patients assigned to placebo, reported Alain Ravaud, MD, PhD from Hôpital Saint André in Bordeaux, France.
“These results represent a major step forward in the clinical management of clear cell renal cell carcinoma,” he said at the European Society for Medical Oncology Congress.
The study was published simultaneously online in the New England Journal of Medicine.
Approximately 16% of all patients with RCC have locoregional (stage III) disease, which is associated with a 5-year survival rate of 53%. Up to 40% of patients with locoregional disease will have a relapse with metastases after nephrectomy, indicating a need for effective adjuvant therapy to reduce the risk of relapse in this population, Dr. Ravaud said.
However, to date, adjuvant therapy with either cytokines, hormones, immunotherapy, or radiotherapy has not been successful at preventing relapse, and the ASSURE trial, comparing sunitinib and sorafenib (Nexavar) with placebo showed that neither of the tyrosine kinase inhibitors (TKIs) improved survival, and each necessitated discontinuations due to toxicity, despite dose reductions, Dr. Ravaud noted.
The trial reported here, S-TRAC (Sunitinib as Adjuvant Treatment for Patients at High Risk of Recurrence of Renal Cell Carcinoma Following Nephrectomy), had different results, however.
A total of 615 patients with high-risk RCC were enrolled. High-risk disease was defined as stage T3, NO or Nx, M0, any Furhman grade and any Eastern Cooperative Oncology Group (ECOG) performance status; T4, N0 or NX, M0, any Fuhrman/ECOG status; or any T, N1-N2, M0, any Fuhrman/ECOG status.
Patients were stratified by risk groups, ECOG status, and country, then randomized to receive either sunitinib 50 mg daily or placebo on a 4 weeks–on, 2 weeks–off schedule for 1 year or until recurrence, unacceptable toxicity, or withdrawal of consent.
Central Reviewers Yes, Investigators No
As noted before, the duration of median DFS, the primary endpoint, was 14 months longer with sunitinib, translating into a hazard ratio (HR) of 0.76 (P = .03). This determination of DFS was performed by central reviewers blinded to treatment type.
However, DFS rates by investigators review, while numerically different between trial arms (6.5 years for sunitinib vs. 4.5 years in the placebo group), were not statistically significant (HR, 0.81, P = .08).
Overall survival data were not mature at the time of the data cutoff, with the median not reached in either group.
Treatment-emergent adverse events were seen in 99.7% of the patients in the sunitinib group and in 88.5% of controls. Investigators attributed adverse events to treatment in 98.4% of patients in the sunitinib arm and 75.7% of those in the placebo arm.
The most common adverse events in the sunitinib group were diarrhea, palmar-plantar erythrodysesthesia, hypertension, fatigue, and nausea.
Grade 3 or higher adverse events were reported in 194 patients (63.4%) in the sunitinib group and in 66 (21.7%) in the placebo group.
Interestingly, there were fewer dose reductions in the sunitinib group (34.3% vs. 46.4%) and fewer dose interruptions (2.0% vs. 13.2%), although more patients on sunitinib discontinued because of adverse events (28.1% vs. 5.6%).
The most common cause of death in each group was RCC, which accounted for 47 of 62 deaths (75.8%) in the sunitinib arm and 47 of 64 (73.4%) in the placebo arm. No death was attributed to treatment-associated toxicities.
Patients on sunitinib also had generally lower scores on quality of life scales, but the between-group differences did not reach the prespecified minimally important difference of 10 patients except for the domains of diarrhea and loss of appetite.
But having said that, he noted that, in S-TRAC as in ASSURE, the study was negative going by investigator rather than central review, and that the positive HR for central review in S-TRAC was near the significance boundary.
Overall, the quality of evidence supporting sunitinib in the adjuvant setting is weak, with benefits barely outweighing harms, and that the cost of the therapy, in light of the above, is high, Dr. Bex said.
He added that he would need to see mature overall survival data from S-TRAC and ASSURE, further results from other ongoing trials with sunitinib, and a positive meta-analysis of studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors in the adjuvant setting before he would change his mind on the use of sunitinib and related agents.
The trial was supported by Pfizer. Dr. Ravaud and Dr. Bex disclosed consulting and research grants from Pfizer and other companies.
COPENHAGEN – In patients with high-risk locoregional clear cell renal cell (RCC) carcinoma, adjuvant therapy with sunitinib significantly prolonged disease-free survival, compared with placebo, reported investigators in a randomized, phase III trial.
Among 615 patients with clear cell RCC at high risk for recurrence following nephrectomy, the median duration of disease-free survival (DFS) by blinded central review was 6.8 years for patients treated with sunitinib (Sutent) for 1 year, compared with 5.6 years for patients assigned to placebo, reported Alain Ravaud, MD, PhD from Hôpital Saint André in Bordeaux, France.
“These results represent a major step forward in the clinical management of clear cell renal cell carcinoma,” he said at the European Society for Medical Oncology Congress.
The study was published simultaneously online in the New England Journal of Medicine.
Approximately 16% of all patients with RCC have locoregional (stage III) disease, which is associated with a 5-year survival rate of 53%. Up to 40% of patients with locoregional disease will have a relapse with metastases after nephrectomy, indicating a need for effective adjuvant therapy to reduce the risk of relapse in this population, Dr. Ravaud said.
However, to date, adjuvant therapy with either cytokines, hormones, immunotherapy, or radiotherapy has not been successful at preventing relapse, and the ASSURE trial, comparing sunitinib and sorafenib (Nexavar) with placebo showed that neither of the tyrosine kinase inhibitors (TKIs) improved survival, and each necessitated discontinuations due to toxicity, despite dose reductions, Dr. Ravaud noted.
The trial reported here, S-TRAC (Sunitinib as Adjuvant Treatment for Patients at High Risk of Recurrence of Renal Cell Carcinoma Following Nephrectomy), had different results, however.
A total of 615 patients with high-risk RCC were enrolled. High-risk disease was defined as stage T3, NO or Nx, M0, any Furhman grade and any Eastern Cooperative Oncology Group (ECOG) performance status; T4, N0 or NX, M0, any Fuhrman/ECOG status; or any T, N1-N2, M0, any Fuhrman/ECOG status.
Patients were stratified by risk groups, ECOG status, and country, then randomized to receive either sunitinib 50 mg daily or placebo on a 4 weeks–on, 2 weeks–off schedule for 1 year or until recurrence, unacceptable toxicity, or withdrawal of consent.
Central Reviewers Yes, Investigators No
As noted before, the duration of median DFS, the primary endpoint, was 14 months longer with sunitinib, translating into a hazard ratio (HR) of 0.76 (P = .03). This determination of DFS was performed by central reviewers blinded to treatment type.
However, DFS rates by investigators review, while numerically different between trial arms (6.5 years for sunitinib vs. 4.5 years in the placebo group), were not statistically significant (HR, 0.81, P = .08).
Overall survival data were not mature at the time of the data cutoff, with the median not reached in either group.
Treatment-emergent adverse events were seen in 99.7% of the patients in the sunitinib group and in 88.5% of controls. Investigators attributed adverse events to treatment in 98.4% of patients in the sunitinib arm and 75.7% of those in the placebo arm.
The most common adverse events in the sunitinib group were diarrhea, palmar-plantar erythrodysesthesia, hypertension, fatigue, and nausea.
Grade 3 or higher adverse events were reported in 194 patients (63.4%) in the sunitinib group and in 66 (21.7%) in the placebo group.
Interestingly, there were fewer dose reductions in the sunitinib group (34.3% vs. 46.4%) and fewer dose interruptions (2.0% vs. 13.2%), although more patients on sunitinib discontinued because of adverse events (28.1% vs. 5.6%).
The most common cause of death in each group was RCC, which accounted for 47 of 62 deaths (75.8%) in the sunitinib arm and 47 of 64 (73.4%) in the placebo arm. No death was attributed to treatment-associated toxicities.
Patients on sunitinib also had generally lower scores on quality of life scales, but the between-group differences did not reach the prespecified minimally important difference of 10 patients except for the domains of diarrhea and loss of appetite.
But having said that, he noted that, in S-TRAC as in ASSURE, the study was negative going by investigator rather than central review, and that the positive HR for central review in S-TRAC was near the significance boundary.
Overall, the quality of evidence supporting sunitinib in the adjuvant setting is weak, with benefits barely outweighing harms, and that the cost of the therapy, in light of the above, is high, Dr. Bex said.
He added that he would need to see mature overall survival data from S-TRAC and ASSURE, further results from other ongoing trials with sunitinib, and a positive meta-analysis of studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors in the adjuvant setting before he would change his mind on the use of sunitinib and related agents.
The trial was supported by Pfizer. Dr. Ravaud and Dr. Bex disclosed consulting and research grants from Pfizer and other companies.
AT ESMO 2016
Key clinical point: S-TRAC is the first clinical trial to show a benefit of adjuvant drug therapy in renal cell carcinoma.
Major finding: The median duration of disease-free survival by central review was 6.8 years for patients randomized to sunitinib vs. 5.6 years for those randomized to placebo.
Data source: Phase III trial of adjuvant therapy following nephrectomy in 615 patients with high-risk clear cell RCC.
Disclosures: The trial was supported by Pfizer. Dr. Ravaud and Dr. Bex disclosed consulting and research grants from Pfizer and other companies.
In favorable intermediate-risk prostate cancer, brachytherapy alone suffices
BOSTON – In a finding hailed as “paradigm changing,” men with favorable intermediate-risk prostate cancer may have good disease control with brachytherapy alone, with fewer late-term toxicities than with brachytherapy combined with external-beam radiation, investigators reported.
After 5 years of follow-up, there were no significant differences in rates of freedom from disease progression among patients assigned to receive combined external-beam radiation (EBRT) and transperineal interstitial permanent brachytherapy (PB) or PB alone in selected patients with intermediate-risk prostatic carcinoma.
“I think you’re underselling your results – I’m pretty excited about these results,” Colleen Lawton, MD, professor and vice chair of radiation oncology at the Medical College of Wisconsin in Milwaukee, told Dr. Prestidge at the annual meeting of the American Society of Radiation Oncology.
The results show that, “for the intermediate-risk group, not the worst of intermediate [risk] but the vast majority, they don’t need the toxicity of that external beam, and they don’t need the cost of it,” she said at a briefing following his presentation of the data in a plenary session.
Dr. Lawton said that, when the NRG Oncology/RTOG 0232study was initiated (the first patients were enrolled in 2003), “there were factions that believed you could not treat intermediate-risk prostate cancer – which isn’t the best, isn’t the worse, but is somewhere in the middle – with anything but the combination, and this shows that’s not true.”
The trial was designed to test the hypothesis that patients with intermediate-risk prostate cancer treated with combined EBRT and PB would have a 10% improvement in freedom from progression (FFP), compared with men treated with PB alone.
A total of 579 patients with histologically confirmed prostate cancer, stages T1c-2b and Zubrod performance score 0 or 1 were enrolled. The patients also had Gleason score 2-6 and prostate-specific antigen (PSA) from 10 to less than 20 ng/mL; Gleason score and PSA less than 10 ng/mL; or prostate volume less than 60 cc.
In addition, androgen deprivation therapy (ADT) was not allowed on the study, and patients could not have distant metastases or radiographically suspicious nodes at the time of enrollment.
Patients were stratified by stage, Gleason score, PSA and history of ADT, and then randomized to the combined therapy, consisting of 45 Gy in a partial pelvis dose delivered in 1.8 Gy fractions for 5 weeks, followed 2-4 weeks later with brachytherapy using either a radioactive iodine (I-125) source prescribed as a 110-Gy boost dose, or palladium 103 in a 100 Gy boost dose; or brachytherapy alone (145-Gy dose with I-I25, 125-Gy dose with palladium 103). EBRT was delivered by either intensity-modulated radiation (43%) or 3D conformal radiation.
Five years after randomization, there were a total of 66 cases of treatment failure (measured as either biochemical failure according to ASTRO criteria, local progression, distant metastases, or death from any cause), 34 occurring in men treated with the combination, and 32 in men treated with brachytherapy alone. Biochemical failures accounted for 68% of events among patients on the combined modalities and 53% of those on brachytherapy alone. There were 9 deaths in the combined arm and 14 deaths in the brachytherapy-only arm, but none were prostate cancer related, Dr. Prestidge said.
In multivariate analysis adjusted for treatment type, age, race, prior hormonal therapy, Gleason/PSA, and tumor stage, the only significant predictor of FFP was Gleason 7/PSA less than 10 ng/mL, which was associated with better outcomes, compared with Gleason score less than 7/PSA 10-20 ng/mL (odds ratio, 0.5; P = .046).
There was no difference in 5-year overall survival between the groups.
As noted before, there were no significant differences in acute toxicities, but there were significantly more late grade 2 or greater toxicities among patients who underwent EBRT and PB (53% vs. 37%; P less than .0001), and more late grade 3 or greater toxicities (12% vs. 7%; P = .039).
Michael J Zelefsky, MD, professor of radiation oncology and chief of the brachytherapy service at Memorial Sloan Kettering Cancer Center in New York, the invited discussant, said that the study suggests that “combining EBRT with brachytherapy for favorable intermediate-risk disease may constitute unnecessary overkill.”
He asserted, however, that favorable intermediate-risk disease behaves clinically more like low-risk disease, whereas unfavorable intermediate-risk disease is closer to high-risk disease in its clinical behavior.
It is plausible that, for patients with unfavorable intermediate-risk disease, added dose intensification associated with combined modality therapy could result in improved FFP and local tumor control, he said.
The study was funded by the National Cancer Institute. Dr. Prestidge disclosed consulting for Varian, Elekta, and IsoRay. Dr. Zelefsky disclosed receiving honoraria from Bebig Brachytherapy, Augmenix, and as editor-in-chief of Brachytherapy. Dr. Lawton reported no relevant disclosures.
BOSTON – In a finding hailed as “paradigm changing,” men with favorable intermediate-risk prostate cancer may have good disease control with brachytherapy alone, with fewer late-term toxicities than with brachytherapy combined with external-beam radiation, investigators reported.
After 5 years of follow-up, there were no significant differences in rates of freedom from disease progression among patients assigned to receive combined external-beam radiation (EBRT) and transperineal interstitial permanent brachytherapy (PB) or PB alone in selected patients with intermediate-risk prostatic carcinoma.
“I think you’re underselling your results – I’m pretty excited about these results,” Colleen Lawton, MD, professor and vice chair of radiation oncology at the Medical College of Wisconsin in Milwaukee, told Dr. Prestidge at the annual meeting of the American Society of Radiation Oncology.
The results show that, “for the intermediate-risk group, not the worst of intermediate [risk] but the vast majority, they don’t need the toxicity of that external beam, and they don’t need the cost of it,” she said at a briefing following his presentation of the data in a plenary session.
Dr. Lawton said that, when the NRG Oncology/RTOG 0232study was initiated (the first patients were enrolled in 2003), “there were factions that believed you could not treat intermediate-risk prostate cancer – which isn’t the best, isn’t the worse, but is somewhere in the middle – with anything but the combination, and this shows that’s not true.”
The trial was designed to test the hypothesis that patients with intermediate-risk prostate cancer treated with combined EBRT and PB would have a 10% improvement in freedom from progression (FFP), compared with men treated with PB alone.
A total of 579 patients with histologically confirmed prostate cancer, stages T1c-2b and Zubrod performance score 0 or 1 were enrolled. The patients also had Gleason score 2-6 and prostate-specific antigen (PSA) from 10 to less than 20 ng/mL; Gleason score and PSA less than 10 ng/mL; or prostate volume less than 60 cc.
In addition, androgen deprivation therapy (ADT) was not allowed on the study, and patients could not have distant metastases or radiographically suspicious nodes at the time of enrollment.
Patients were stratified by stage, Gleason score, PSA and history of ADT, and then randomized to the combined therapy, consisting of 45 Gy in a partial pelvis dose delivered in 1.8 Gy fractions for 5 weeks, followed 2-4 weeks later with brachytherapy using either a radioactive iodine (I-125) source prescribed as a 110-Gy boost dose, or palladium 103 in a 100 Gy boost dose; or brachytherapy alone (145-Gy dose with I-I25, 125-Gy dose with palladium 103). EBRT was delivered by either intensity-modulated radiation (43%) or 3D conformal radiation.
Five years after randomization, there were a total of 66 cases of treatment failure (measured as either biochemical failure according to ASTRO criteria, local progression, distant metastases, or death from any cause), 34 occurring in men treated with the combination, and 32 in men treated with brachytherapy alone. Biochemical failures accounted for 68% of events among patients on the combined modalities and 53% of those on brachytherapy alone. There were 9 deaths in the combined arm and 14 deaths in the brachytherapy-only arm, but none were prostate cancer related, Dr. Prestidge said.
In multivariate analysis adjusted for treatment type, age, race, prior hormonal therapy, Gleason/PSA, and tumor stage, the only significant predictor of FFP was Gleason 7/PSA less than 10 ng/mL, which was associated with better outcomes, compared with Gleason score less than 7/PSA 10-20 ng/mL (odds ratio, 0.5; P = .046).
There was no difference in 5-year overall survival between the groups.
As noted before, there were no significant differences in acute toxicities, but there were significantly more late grade 2 or greater toxicities among patients who underwent EBRT and PB (53% vs. 37%; P less than .0001), and more late grade 3 or greater toxicities (12% vs. 7%; P = .039).
Michael J Zelefsky, MD, professor of radiation oncology and chief of the brachytherapy service at Memorial Sloan Kettering Cancer Center in New York, the invited discussant, said that the study suggests that “combining EBRT with brachytherapy for favorable intermediate-risk disease may constitute unnecessary overkill.”
He asserted, however, that favorable intermediate-risk disease behaves clinically more like low-risk disease, whereas unfavorable intermediate-risk disease is closer to high-risk disease in its clinical behavior.
It is plausible that, for patients with unfavorable intermediate-risk disease, added dose intensification associated with combined modality therapy could result in improved FFP and local tumor control, he said.
The study was funded by the National Cancer Institute. Dr. Prestidge disclosed consulting for Varian, Elekta, and IsoRay. Dr. Zelefsky disclosed receiving honoraria from Bebig Brachytherapy, Augmenix, and as editor-in-chief of Brachytherapy. Dr. Lawton reported no relevant disclosures.
BOSTON – In a finding hailed as “paradigm changing,” men with favorable intermediate-risk prostate cancer may have good disease control with brachytherapy alone, with fewer late-term toxicities than with brachytherapy combined with external-beam radiation, investigators reported.
After 5 years of follow-up, there were no significant differences in rates of freedom from disease progression among patients assigned to receive combined external-beam radiation (EBRT) and transperineal interstitial permanent brachytherapy (PB) or PB alone in selected patients with intermediate-risk prostatic carcinoma.
“I think you’re underselling your results – I’m pretty excited about these results,” Colleen Lawton, MD, professor and vice chair of radiation oncology at the Medical College of Wisconsin in Milwaukee, told Dr. Prestidge at the annual meeting of the American Society of Radiation Oncology.
The results show that, “for the intermediate-risk group, not the worst of intermediate [risk] but the vast majority, they don’t need the toxicity of that external beam, and they don’t need the cost of it,” she said at a briefing following his presentation of the data in a plenary session.
Dr. Lawton said that, when the NRG Oncology/RTOG 0232study was initiated (the first patients were enrolled in 2003), “there were factions that believed you could not treat intermediate-risk prostate cancer – which isn’t the best, isn’t the worse, but is somewhere in the middle – with anything but the combination, and this shows that’s not true.”
The trial was designed to test the hypothesis that patients with intermediate-risk prostate cancer treated with combined EBRT and PB would have a 10% improvement in freedom from progression (FFP), compared with men treated with PB alone.
A total of 579 patients with histologically confirmed prostate cancer, stages T1c-2b and Zubrod performance score 0 or 1 were enrolled. The patients also had Gleason score 2-6 and prostate-specific antigen (PSA) from 10 to less than 20 ng/mL; Gleason score and PSA less than 10 ng/mL; or prostate volume less than 60 cc.
In addition, androgen deprivation therapy (ADT) was not allowed on the study, and patients could not have distant metastases or radiographically suspicious nodes at the time of enrollment.
Patients were stratified by stage, Gleason score, PSA and history of ADT, and then randomized to the combined therapy, consisting of 45 Gy in a partial pelvis dose delivered in 1.8 Gy fractions for 5 weeks, followed 2-4 weeks later with brachytherapy using either a radioactive iodine (I-125) source prescribed as a 110-Gy boost dose, or palladium 103 in a 100 Gy boost dose; or brachytherapy alone (145-Gy dose with I-I25, 125-Gy dose with palladium 103). EBRT was delivered by either intensity-modulated radiation (43%) or 3D conformal radiation.
Five years after randomization, there were a total of 66 cases of treatment failure (measured as either biochemical failure according to ASTRO criteria, local progression, distant metastases, or death from any cause), 34 occurring in men treated with the combination, and 32 in men treated with brachytherapy alone. Biochemical failures accounted for 68% of events among patients on the combined modalities and 53% of those on brachytherapy alone. There were 9 deaths in the combined arm and 14 deaths in the brachytherapy-only arm, but none were prostate cancer related, Dr. Prestidge said.
In multivariate analysis adjusted for treatment type, age, race, prior hormonal therapy, Gleason/PSA, and tumor stage, the only significant predictor of FFP was Gleason 7/PSA less than 10 ng/mL, which was associated with better outcomes, compared with Gleason score less than 7/PSA 10-20 ng/mL (odds ratio, 0.5; P = .046).
There was no difference in 5-year overall survival between the groups.
As noted before, there were no significant differences in acute toxicities, but there were significantly more late grade 2 or greater toxicities among patients who underwent EBRT and PB (53% vs. 37%; P less than .0001), and more late grade 3 or greater toxicities (12% vs. 7%; P = .039).
Michael J Zelefsky, MD, professor of radiation oncology and chief of the brachytherapy service at Memorial Sloan Kettering Cancer Center in New York, the invited discussant, said that the study suggests that “combining EBRT with brachytherapy for favorable intermediate-risk disease may constitute unnecessary overkill.”
He asserted, however, that favorable intermediate-risk disease behaves clinically more like low-risk disease, whereas unfavorable intermediate-risk disease is closer to high-risk disease in its clinical behavior.
It is plausible that, for patients with unfavorable intermediate-risk disease, added dose intensification associated with combined modality therapy could result in improved FFP and local tumor control, he said.
The study was funded by the National Cancer Institute. Dr. Prestidge disclosed consulting for Varian, Elekta, and IsoRay. Dr. Zelefsky disclosed receiving honoraria from Bebig Brachytherapy, Augmenix, and as editor-in-chief of Brachytherapy. Dr. Lawton reported no relevant disclosures.
AT ASTRO 2016
Key clinical point: It may be clinically unnecessary to add external-beam radiation to brachytherapy in men with favorable intermediate-risk prostate cancer.
Major finding: Outcomes were comparable for men with favorable intermediate-risk prostate cancer treated with external-beam radiation plus brachytherapy or brachytherapy alone.
Data source: Randomized, controlled trial in 579 men with intermediate-risk prostate cancer.
Disclosures: The study was funded by the National Cancer Institute. Dr. Prestidge disclosed consulting for Varian, Elekta, and IsoRay. Dr. Zelefsky disclosed receiving honoraria from Bebig Brachytherapy, Augmenix, and as editor-in-chief of Brachytherapy. Dr. Lawton reported no relevant disclosures.
Hypofractionated RT safe, convenient in low-risk prostate cancer
BOSTON – Shortening the radiation dosing schedule by 3 weeks in men with early-stage, low-risk prostate cancer does not appear to result in worse outcomes or diminished quality of life, according to investigators in the NRG Oncology/RTOG 0415 trial.
Efficacy results from the trial, reported at the annual meeting of the American Society for Radiation Oncology, showed that a radiation schedule of 70 Gy in 28 fractions delivered over 5.6 weeks was not inferior to 73.8 Gy delivered in 41 fractions over 8.2 weeks in terms of disease-free, progression-free, or overall survival.
“The International Atomic Energy [Agency] in its prostate cancer guidelines still lists hypofractionated radiation therapy as investigational, but I think we are at the stage where there is a ton of evidence, and this is really no leap of faith anymore that this can become the standard of care,” said Deborah W. Bruner, PhD, of Emory University and the Winship Cancer Institute in Atlanta.
In the treatment of patients with low-risk prostate cancer who opt for therapy over active surveillance, it is essential that “we treat them with the absolute minimum amount of treatment, with minimum side effects, and with minimum cost,” she said at a plenary session.
As reported by the investigators in 2015, there were small but significant increases in clinician-reported adverse gastrointestinal and genitourinary adverse events in the hypofractionation arm compared with the conventional fractionation arm in the trial, prompting the researchers to see whether patients were actually experiencing what clinicians thought they were seeing.
The investigators examined health-related quality of life and symptoms using the Expanded Prostate Index Composite (EPIC instrument).
They used a 50-item patient-reported outcomes questionnaire using a scale of 0 (no problem) to 4 (big problem), with responses transferred to a 0-100 scale. The questionnaire asked about symptoms in four domains: bowel, urinary, sexual, and hormonal. Patients filled out the questionnaire at baseline and at 6 and 12 months of follow-up.
At 1 year, there were no changes from baseline in hormonal scores in either study arm, but sexual function scores declined by approximately 15 points among patients treated with conventional fractionation and by 11 points among patients treated with hypofractionation (between-group difference nonsignificant).
There was a small decline in urinary scores in both arms, but this difference was not significant.
Patients treated with hypofractionation had a statistically larger decline in bowel scores compared with patients treated with conventional fractionation, a 1.8-point difference, but this difference did not translate into a clinically significant difference; that is, patients themselves could not detect a significant decline in bowel function, Dr. Bruner said.
The invited discussant, Ronald Chen, MD, MPH, director of the comparative effectiveness research program at the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, agreed that a difference of only 1.8 points on a 0-100 scale, while technically significant, is clinically meaningless.
“So now we have the complete story and a better understanding of perhaps the value of hypofractionation versus standard fractionation from the patient’s perspective,” he said.
He also emphasized that “quality of life is a central component of any value framework in cancer care, and we must hear the patient’s voice. For clinical trials to truly inform patient decision making and allow patients to assess the value of their treatment options, quality of life must be studied.”
BOSTON – Shortening the radiation dosing schedule by 3 weeks in men with early-stage, low-risk prostate cancer does not appear to result in worse outcomes or diminished quality of life, according to investigators in the NRG Oncology/RTOG 0415 trial.
Efficacy results from the trial, reported at the annual meeting of the American Society for Radiation Oncology, showed that a radiation schedule of 70 Gy in 28 fractions delivered over 5.6 weeks was not inferior to 73.8 Gy delivered in 41 fractions over 8.2 weeks in terms of disease-free, progression-free, or overall survival.
“The International Atomic Energy [Agency] in its prostate cancer guidelines still lists hypofractionated radiation therapy as investigational, but I think we are at the stage where there is a ton of evidence, and this is really no leap of faith anymore that this can become the standard of care,” said Deborah W. Bruner, PhD, of Emory University and the Winship Cancer Institute in Atlanta.
In the treatment of patients with low-risk prostate cancer who opt for therapy over active surveillance, it is essential that “we treat them with the absolute minimum amount of treatment, with minimum side effects, and with minimum cost,” she said at a plenary session.
As reported by the investigators in 2015, there were small but significant increases in clinician-reported adverse gastrointestinal and genitourinary adverse events in the hypofractionation arm compared with the conventional fractionation arm in the trial, prompting the researchers to see whether patients were actually experiencing what clinicians thought they were seeing.
The investigators examined health-related quality of life and symptoms using the Expanded Prostate Index Composite (EPIC instrument).
They used a 50-item patient-reported outcomes questionnaire using a scale of 0 (no problem) to 4 (big problem), with responses transferred to a 0-100 scale. The questionnaire asked about symptoms in four domains: bowel, urinary, sexual, and hormonal. Patients filled out the questionnaire at baseline and at 6 and 12 months of follow-up.
At 1 year, there were no changes from baseline in hormonal scores in either study arm, but sexual function scores declined by approximately 15 points among patients treated with conventional fractionation and by 11 points among patients treated with hypofractionation (between-group difference nonsignificant).
There was a small decline in urinary scores in both arms, but this difference was not significant.
Patients treated with hypofractionation had a statistically larger decline in bowel scores compared with patients treated with conventional fractionation, a 1.8-point difference, but this difference did not translate into a clinically significant difference; that is, patients themselves could not detect a significant decline in bowel function, Dr. Bruner said.
The invited discussant, Ronald Chen, MD, MPH, director of the comparative effectiveness research program at the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, agreed that a difference of only 1.8 points on a 0-100 scale, while technically significant, is clinically meaningless.
“So now we have the complete story and a better understanding of perhaps the value of hypofractionation versus standard fractionation from the patient’s perspective,” he said.
He also emphasized that “quality of life is a central component of any value framework in cancer care, and we must hear the patient’s voice. For clinical trials to truly inform patient decision making and allow patients to assess the value of their treatment options, quality of life must be studied.”
BOSTON – Shortening the radiation dosing schedule by 3 weeks in men with early-stage, low-risk prostate cancer does not appear to result in worse outcomes or diminished quality of life, according to investigators in the NRG Oncology/RTOG 0415 trial.
Efficacy results from the trial, reported at the annual meeting of the American Society for Radiation Oncology, showed that a radiation schedule of 70 Gy in 28 fractions delivered over 5.6 weeks was not inferior to 73.8 Gy delivered in 41 fractions over 8.2 weeks in terms of disease-free, progression-free, or overall survival.
“The International Atomic Energy [Agency] in its prostate cancer guidelines still lists hypofractionated radiation therapy as investigational, but I think we are at the stage where there is a ton of evidence, and this is really no leap of faith anymore that this can become the standard of care,” said Deborah W. Bruner, PhD, of Emory University and the Winship Cancer Institute in Atlanta.
In the treatment of patients with low-risk prostate cancer who opt for therapy over active surveillance, it is essential that “we treat them with the absolute minimum amount of treatment, with minimum side effects, and with minimum cost,” she said at a plenary session.
As reported by the investigators in 2015, there were small but significant increases in clinician-reported adverse gastrointestinal and genitourinary adverse events in the hypofractionation arm compared with the conventional fractionation arm in the trial, prompting the researchers to see whether patients were actually experiencing what clinicians thought they were seeing.
The investigators examined health-related quality of life and symptoms using the Expanded Prostate Index Composite (EPIC instrument).
They used a 50-item patient-reported outcomes questionnaire using a scale of 0 (no problem) to 4 (big problem), with responses transferred to a 0-100 scale. The questionnaire asked about symptoms in four domains: bowel, urinary, sexual, and hormonal. Patients filled out the questionnaire at baseline and at 6 and 12 months of follow-up.
At 1 year, there were no changes from baseline in hormonal scores in either study arm, but sexual function scores declined by approximately 15 points among patients treated with conventional fractionation and by 11 points among patients treated with hypofractionation (between-group difference nonsignificant).
There was a small decline in urinary scores in both arms, but this difference was not significant.
Patients treated with hypofractionation had a statistically larger decline in bowel scores compared with patients treated with conventional fractionation, a 1.8-point difference, but this difference did not translate into a clinically significant difference; that is, patients themselves could not detect a significant decline in bowel function, Dr. Bruner said.
The invited discussant, Ronald Chen, MD, MPH, director of the comparative effectiveness research program at the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, agreed that a difference of only 1.8 points on a 0-100 scale, while technically significant, is clinically meaningless.
“So now we have the complete story and a better understanding of perhaps the value of hypofractionation versus standard fractionation from the patient’s perspective,” he said.
He also emphasized that “quality of life is a central component of any value framework in cancer care, and we must hear the patient’s voice. For clinical trials to truly inform patient decision making and allow patients to assess the value of their treatment options, quality of life must be studied.”
Key clinical point: There were no clinically significant differences in survival or patient-reported outcomes between hypofractionated or conventional radiation schedules for patients with low-risk prostate cancer.
Major finding: There was statistically but not clinically significant difference of 1.8 out of 100 patients on a quality-of-life scale.
Data source: Analysis of patient-reported QoL in the NRG//RTOG 0415 trial.
Disclosures: The National Cancer Institute supported the study. Dr. Bruner and Dr. Chen reported having no conflicts of interest.
Prostate cancer recurrence rates low with SBRT
BOSTON – For men with newly diagnosed low- or intermediate-risk prostate cancer, stereotactic body radiotherapy (SBRT) in the right hands can be safe, with low radiation-associated toxicities and with cancer control rates that compare favorably with those produced with external-beam radiotherapy (EBRT), investigators in a multicenter study report.
At 5-year follow-up, there were no grade 4 toxicities, no treatment-related deaths, and just five grade 3 adverse events that occurred in 4 out of 309 patients treated with SBRT, said Robert Meier, MD, at the annual meeting of the American Society for Radiation Oncology.
Using a standard radiology definition of recurrence as a more than 2 ng/mL increase in prostate-specific antigen (PSA) levels over posttreatment nadir, 97.1% of all patients were recurrence free at 5 years.
Among 172 patients with low-risk disease (T1b-T2, Gleason 6 or less and PSA 10 ng/mL or less), 97.3% were recurrence-free at 5 years, which compares favorably with the 93% seen in combined data from three large clinical trials of dose-escalated EBRT, Dr. Meier said.
For the 137 patients with intermediate risk disease (T1B-T2b, Gleason = 7, and PSA of 10 or less, or Gleason 6 or lower with a PSA between 10 and 20), 97% were recurrence-free at 5 years, a result “that matches the best results in radiotherapy for intermediate-risk patients, and matches the best results for, for example, dose-escalated IMRT [intensity-modulated radiation therapy],” he commented.
“The data is very encouraging,” commented Colleen Lawton, MD, professor and vice chair of radiation oncology at the Medical College of Wisconsin in Milwaukee.
To determine the safety and efficacy of SBRT in men with newly diagnosed prostate cancer, Dr. Meier and coinvestigators at six centers in the United States designed a prospective study.
A total of 309 patients were enrolled, and all were treated with SBRT delivered in 5 fractions of 8 Gy each over 5 days with a robotic linear accelerator that tracks the prostate, and corrections for motion in three spatial dimension, as well as yaw, pitch, and roll.
The treatment-delivery pattern is shaped to constrain doses to the bladder, rectum, testes, and penile bulb.
Using standard dosimetry calculation, the total actual radiation dose delivered to the prostate is equivalent to approximately 100 Gy, Dr. Meier said.
The safety analysis was powered to consider a greater than 10% rate of grade 3-5 urinary or bowel side effects as excessive. The efficacy analysis was designed to ask whether 5-year recurrence-free rates in low-risk patients could equal or be superior to a historical control rate of 93%.
As noted before, there were no grade 4 toxicities and no treatment-related deaths, and the rate of grade 3 side effects was 2.7%. with two events occurring in low-risk patients, and three in intermediate-risk patients. The events, all genitourinary toxicities, occurred from 11 to 51 months after treatment. Grade 1 or 2 genitourinary toxicities at any time were seen in 53% and 35% of patients, respectively. Grade 1 or 2 GI toxicities were seen in 59% and 10%.
Five patients developed urinary retention which required temporary catheter placement.
The ideal candidate for the therapy is the unfavorable intermediate-risk patient, Dr. Meier said in the interview.
“These are the patients who, if they are going to get external-beam radiation, have to combine it with androgen ablation, and that has its own toxicities. SBRT did very well even in the unfavorable intermediate-risk patients, so I think that group, and for that matter any intermediate-risk patient, is ideally suited,” he said.
The study was supported by Accuray. Dr. Meier disclosed research grants from the company. Dr. Lawton reported no relevant financial disclosures.
BOSTON – For men with newly diagnosed low- or intermediate-risk prostate cancer, stereotactic body radiotherapy (SBRT) in the right hands can be safe, with low radiation-associated toxicities and with cancer control rates that compare favorably with those produced with external-beam radiotherapy (EBRT), investigators in a multicenter study report.
At 5-year follow-up, there were no grade 4 toxicities, no treatment-related deaths, and just five grade 3 adverse events that occurred in 4 out of 309 patients treated with SBRT, said Robert Meier, MD, at the annual meeting of the American Society for Radiation Oncology.
Using a standard radiology definition of recurrence as a more than 2 ng/mL increase in prostate-specific antigen (PSA) levels over posttreatment nadir, 97.1% of all patients were recurrence free at 5 years.
Among 172 patients with low-risk disease (T1b-T2, Gleason 6 or less and PSA 10 ng/mL or less), 97.3% were recurrence-free at 5 years, which compares favorably with the 93% seen in combined data from three large clinical trials of dose-escalated EBRT, Dr. Meier said.
For the 137 patients with intermediate risk disease (T1B-T2b, Gleason = 7, and PSA of 10 or less, or Gleason 6 or lower with a PSA between 10 and 20), 97% were recurrence-free at 5 years, a result “that matches the best results in radiotherapy for intermediate-risk patients, and matches the best results for, for example, dose-escalated IMRT [intensity-modulated radiation therapy],” he commented.
“The data is very encouraging,” commented Colleen Lawton, MD, professor and vice chair of radiation oncology at the Medical College of Wisconsin in Milwaukee.
To determine the safety and efficacy of SBRT in men with newly diagnosed prostate cancer, Dr. Meier and coinvestigators at six centers in the United States designed a prospective study.
A total of 309 patients were enrolled, and all were treated with SBRT delivered in 5 fractions of 8 Gy each over 5 days with a robotic linear accelerator that tracks the prostate, and corrections for motion in three spatial dimension, as well as yaw, pitch, and roll.
The treatment-delivery pattern is shaped to constrain doses to the bladder, rectum, testes, and penile bulb.
Using standard dosimetry calculation, the total actual radiation dose delivered to the prostate is equivalent to approximately 100 Gy, Dr. Meier said.
The safety analysis was powered to consider a greater than 10% rate of grade 3-5 urinary or bowel side effects as excessive. The efficacy analysis was designed to ask whether 5-year recurrence-free rates in low-risk patients could equal or be superior to a historical control rate of 93%.
As noted before, there were no grade 4 toxicities and no treatment-related deaths, and the rate of grade 3 side effects was 2.7%. with two events occurring in low-risk patients, and three in intermediate-risk patients. The events, all genitourinary toxicities, occurred from 11 to 51 months after treatment. Grade 1 or 2 genitourinary toxicities at any time were seen in 53% and 35% of patients, respectively. Grade 1 or 2 GI toxicities were seen in 59% and 10%.
Five patients developed urinary retention which required temporary catheter placement.
The ideal candidate for the therapy is the unfavorable intermediate-risk patient, Dr. Meier said in the interview.
“These are the patients who, if they are going to get external-beam radiation, have to combine it with androgen ablation, and that has its own toxicities. SBRT did very well even in the unfavorable intermediate-risk patients, so I think that group, and for that matter any intermediate-risk patient, is ideally suited,” he said.
The study was supported by Accuray. Dr. Meier disclosed research grants from the company. Dr. Lawton reported no relevant financial disclosures.
BOSTON – For men with newly diagnosed low- or intermediate-risk prostate cancer, stereotactic body radiotherapy (SBRT) in the right hands can be safe, with low radiation-associated toxicities and with cancer control rates that compare favorably with those produced with external-beam radiotherapy (EBRT), investigators in a multicenter study report.
At 5-year follow-up, there were no grade 4 toxicities, no treatment-related deaths, and just five grade 3 adverse events that occurred in 4 out of 309 patients treated with SBRT, said Robert Meier, MD, at the annual meeting of the American Society for Radiation Oncology.
Using a standard radiology definition of recurrence as a more than 2 ng/mL increase in prostate-specific antigen (PSA) levels over posttreatment nadir, 97.1% of all patients were recurrence free at 5 years.
Among 172 patients with low-risk disease (T1b-T2, Gleason 6 or less and PSA 10 ng/mL or less), 97.3% were recurrence-free at 5 years, which compares favorably with the 93% seen in combined data from three large clinical trials of dose-escalated EBRT, Dr. Meier said.
For the 137 patients with intermediate risk disease (T1B-T2b, Gleason = 7, and PSA of 10 or less, or Gleason 6 or lower with a PSA between 10 and 20), 97% were recurrence-free at 5 years, a result “that matches the best results in radiotherapy for intermediate-risk patients, and matches the best results for, for example, dose-escalated IMRT [intensity-modulated radiation therapy],” he commented.
“The data is very encouraging,” commented Colleen Lawton, MD, professor and vice chair of radiation oncology at the Medical College of Wisconsin in Milwaukee.
To determine the safety and efficacy of SBRT in men with newly diagnosed prostate cancer, Dr. Meier and coinvestigators at six centers in the United States designed a prospective study.
A total of 309 patients were enrolled, and all were treated with SBRT delivered in 5 fractions of 8 Gy each over 5 days with a robotic linear accelerator that tracks the prostate, and corrections for motion in three spatial dimension, as well as yaw, pitch, and roll.
The treatment-delivery pattern is shaped to constrain doses to the bladder, rectum, testes, and penile bulb.
Using standard dosimetry calculation, the total actual radiation dose delivered to the prostate is equivalent to approximately 100 Gy, Dr. Meier said.
The safety analysis was powered to consider a greater than 10% rate of grade 3-5 urinary or bowel side effects as excessive. The efficacy analysis was designed to ask whether 5-year recurrence-free rates in low-risk patients could equal or be superior to a historical control rate of 93%.
As noted before, there were no grade 4 toxicities and no treatment-related deaths, and the rate of grade 3 side effects was 2.7%. with two events occurring in low-risk patients, and three in intermediate-risk patients. The events, all genitourinary toxicities, occurred from 11 to 51 months after treatment. Grade 1 or 2 genitourinary toxicities at any time were seen in 53% and 35% of patients, respectively. Grade 1 or 2 GI toxicities were seen in 59% and 10%.
Five patients developed urinary retention which required temporary catheter placement.
The ideal candidate for the therapy is the unfavorable intermediate-risk patient, Dr. Meier said in the interview.
“These are the patients who, if they are going to get external-beam radiation, have to combine it with androgen ablation, and that has its own toxicities. SBRT did very well even in the unfavorable intermediate-risk patients, so I think that group, and for that matter any intermediate-risk patient, is ideally suited,” he said.
The study was supported by Accuray. Dr. Meier disclosed research grants from the company. Dr. Lawton reported no relevant financial disclosures.
Key clinical point:
Major finding: The 5-year recurrence-free rate for low-risk patients was 97.3%, surpassing the 93% seen with historic controls.
Data source: Prospective study in 309 patients treated at six U.S. centers.
Disclosures: The study was supported by Accuray. Dr. Meier disclosed research grants from the company. Dr. Lawton reported no relevant financial disclosures.
A positive attitude in prostate cancer challenges: finding hope and optimism
Background Prostate cancer affects not only men with the disease, but their partners and families as well. These affects can include changes to everyday lifestyle activities, incontinence, and sexual dysfunction, and sometimes, relationships.
Objective To find out how men with prostate cancer and their female partners found spiritual lift and hope during the prostate cancer trajectory.
Methods The very personal and human nature of the question suggested that a qualitative approach with narrative inquiry would be the most appropriate. Comments were obtained from 10 men and 10 women who were not in a relationship with each other and from 10 couples (N = 40) and then subjected to narrative and thematic analysis.
Results The participants’ activities and circumstances provided their lift – rising above the everyday mundane – and their hope – optimism for the future – and helped them cope. In addition, what emerged was interesting insights on the way in which the participants associated these concepts with having a positive attitude in their life. They provided some valuable information on what constitutes being positive that will be helpful to others in similar circumstances, and to health professionals.
Limitations The information from a relatively small number of participants needs to be interpreted carefully and cannot result in strong conclusions about the nature of the results.
Conclusions Being positive during a time of illness and when dealing with the consequences of the illness, is an important element in coping. However, an understanding of the practicalities of what it means to be positive needs to be thoroughly developed and understood.
Click on the PDF icon at the top of this introduction to read the full article.
Background Prostate cancer affects not only men with the disease, but their partners and families as well. These affects can include changes to everyday lifestyle activities, incontinence, and sexual dysfunction, and sometimes, relationships.
Objective To find out how men with prostate cancer and their female partners found spiritual lift and hope during the prostate cancer trajectory.
Methods The very personal and human nature of the question suggested that a qualitative approach with narrative inquiry would be the most appropriate. Comments were obtained from 10 men and 10 women who were not in a relationship with each other and from 10 couples (N = 40) and then subjected to narrative and thematic analysis.
Results The participants’ activities and circumstances provided their lift – rising above the everyday mundane – and their hope – optimism for the future – and helped them cope. In addition, what emerged was interesting insights on the way in which the participants associated these concepts with having a positive attitude in their life. They provided some valuable information on what constitutes being positive that will be helpful to others in similar circumstances, and to health professionals.
Limitations The information from a relatively small number of participants needs to be interpreted carefully and cannot result in strong conclusions about the nature of the results.
Conclusions Being positive during a time of illness and when dealing with the consequences of the illness, is an important element in coping. However, an understanding of the practicalities of what it means to be positive needs to be thoroughly developed and understood.
Click on the PDF icon at the top of this introduction to read the full article.
Background Prostate cancer affects not only men with the disease, but their partners and families as well. These affects can include changes to everyday lifestyle activities, incontinence, and sexual dysfunction, and sometimes, relationships.
Objective To find out how men with prostate cancer and their female partners found spiritual lift and hope during the prostate cancer trajectory.
Methods The very personal and human nature of the question suggested that a qualitative approach with narrative inquiry would be the most appropriate. Comments were obtained from 10 men and 10 women who were not in a relationship with each other and from 10 couples (N = 40) and then subjected to narrative and thematic analysis.
Results The participants’ activities and circumstances provided their lift – rising above the everyday mundane – and their hope – optimism for the future – and helped them cope. In addition, what emerged was interesting insights on the way in which the participants associated these concepts with having a positive attitude in their life. They provided some valuable information on what constitutes being positive that will be helpful to others in similar circumstances, and to health professionals.
Limitations The information from a relatively small number of participants needs to be interpreted carefully and cannot result in strong conclusions about the nature of the results.
Conclusions Being positive during a time of illness and when dealing with the consequences of the illness, is an important element in coping. However, an understanding of the practicalities of what it means to be positive needs to be thoroughly developed and understood.
Click on the PDF icon at the top of this introduction to read the full article.
Evaluation of a policy of lymph node retrieval for colon cancer specimens: a quality improvement opportunity
10-year follow-up: Localized prostate cancer treatments offer similar efficacy
The three main approaches for treating localized prostate cancer – surgery, radiotherapy, or active monitoring – yield similar efficacy outcomes but different quality-of-life outcomes, according to two reports published on the New England Journal of Medicine.
Both reports present the findings of the ongoing Protect (Prostate Testing for Cancer and Treatment) trial, a large prospective, randomized trial in the United Kingdom comparing mortality and other health outcomes in men with PSA-detected localized disease. The trial involved 82,429 men aged 50-69 years who had a PSA test between 1999 and 2009, of whom 2,664 were found to have localized prostate cancer. A total of 1,643 of these participants agreed to be randomly assigned to radical prostatectomy (553 men), radical radiotherapy (545 men), or active monitoring (545 men).
“Active monitoring” involved avoiding any immediate therapy and regularly monitoring disease progression so that radical treatment with curative intent could be given if the need arose. Patients were monitored every 3 months for the first year, then every 6-12 months thereafter. This differs from “watchful waiting,” which doesn’t involve any plan for curative radical treatment if disease progresses.
The first report focused on mortality and disease progression in these 1,643 participants at a median of 10 years of follow-up. The primary outcome measure, prostate cancer–specific survival, was 98.8% or greater across all three study groups, and there was no significant difference among them. Thus, all three approaches yielded the same efficacy: prostate cancer–specific mortality of approximately 1%, said Freddie C. Hamdy, MD, of the Nuffield Department of Surgical Sciences, University of Oxford, and his associates.
However, the rate of disease progression among men assigned to surgery (8.9/1,000 person-years) or to radiotherapy (9.0/1,000 person-years) was less than half the rate among men assigned to active monitoring (22.9/1,000 person-years). The rate of metastasis followed this same pattern (2.4, 3.0, and 6.3 per 1,000 person-years, respectively).
“These differences show the effectiveness of immediate radical therapy over active monitoring, but they have not translated into significant differences – nor have they ruled out equivalence – in disease-specific or all-cause mortality; thus, longer-term follow-up is necessary,” Dr. Hamdy and his associates said (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606220).
The trade-off was that 44% of the men assigned to active monitoring were able to forgo both radical surgery and radical radiotherapy, avoiding the adverse effects of those treatments. These included nine thromboembolic or cardiovascular events, 14 transfusions, one rectal injury, and nine anastomotic problems requiring intervention, they noted.
It is important to remember that approximately one-fourth of the men assigned to active monitoring went on to undergo radical treatment within 3 years, and that more than half did so by the 10-year follow-up date, the investigators added.
The second report focused on patient-reported outcomes concerning urinary, bowel, sexual, and quality-of-life issues in the 1,643 participants at 6 years of follow-up. These differed markedly among the three study groups, said Jenny L. Donovan, PhD, of the School of Social and Community Medicine, University of Bristol, U.K., and her associates.
Prostatectomy had a clear negative effect on urinary continence and sexual function, particularly erectile function, compared with radiotherapy and active monitoring. This peaked at 6 months after surgery, and though some patients recovered some function over time, urinary incontinence remained worse in the prostatectomy group than in the other two groups throughout follow-up. The use of absorbent pads rose from 1% at baseline to 46% at 6 months in the prostatectomy group. In comparison, the 6-month rate in the radiotherapy group rose to only 5% and that in the active-monitoring group to only 4%.
Radiotherapy plus neoadjuvant androgen-deprivation therapy had more of a negative effect on bowel function, urinary voiding, and nocturia than did the other two treatment approaches. However, many patients eventually showed considerable recovery on most of these measures, except that they continued to have bloody stools more frequently than did men who had prostatectomy or active monitoring.
Men in the active-monitoring group had substantially less difficulty with urinary, sexual, and bowel function, as expected. However, this gradually worsened over time as increasing numbers of these men eventually underwent radical treatments, Dr. Donovan and her associates wrote (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606221).
Quality-of-life measures generally reflected these differences among the three study groups, “with some evidence of accommodation to changes over time.” General mental and physical health, cancer-specific quality of life, and anxiety and depression all were similar across the three groups at 6 years.
“Follow-up for an additional 5-10 years is required to fully inform decisions involving the trade-off between the shorter-term effects of the management strategies shown here and the longer course of progression and treatment of prostate cancer in the context of other life-threatening conditions,” they said.
The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.
As both groups of researchers noted, longer follow-up is needed to definitively assess outcomes in the Protect trial. For now, however, we can conclude that active monitoring leads to increased metastasis, compared with either surgery or radiotherapy.
So if a man wants to avoid metastatic prostate cancer and the adverse effects of its treatment, active monitoring should be considered only if he has life-shortening, coexisting disease and his life expectancy is less than the 10-year median follow-up of this study.
Men who have low- or intermediate-risk prostate cancer should feel free to select either surgery or radiotherapy on the basis of the treatments’ QOL profiles, since the mortality profiles are equivalent.
Anthony V. D’Amico, MD, is in the department of radiation oncology at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, both in Boston. He reported having no relevant financial disclosures. Dr. D’Amico made these remarks in an editorial accompanying the two reports on the Protect trial (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEHMe1610395).
As both groups of researchers noted, longer follow-up is needed to definitively assess outcomes in the Protect trial. For now, however, we can conclude that active monitoring leads to increased metastasis, compared with either surgery or radiotherapy.
So if a man wants to avoid metastatic prostate cancer and the adverse effects of its treatment, active monitoring should be considered only if he has life-shortening, coexisting disease and his life expectancy is less than the 10-year median follow-up of this study.
Men who have low- or intermediate-risk prostate cancer should feel free to select either surgery or radiotherapy on the basis of the treatments’ QOL profiles, since the mortality profiles are equivalent.
Anthony V. D’Amico, MD, is in the department of radiation oncology at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, both in Boston. He reported having no relevant financial disclosures. Dr. D’Amico made these remarks in an editorial accompanying the two reports on the Protect trial (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEHMe1610395).
As both groups of researchers noted, longer follow-up is needed to definitively assess outcomes in the Protect trial. For now, however, we can conclude that active monitoring leads to increased metastasis, compared with either surgery or radiotherapy.
So if a man wants to avoid metastatic prostate cancer and the adverse effects of its treatment, active monitoring should be considered only if he has life-shortening, coexisting disease and his life expectancy is less than the 10-year median follow-up of this study.
Men who have low- or intermediate-risk prostate cancer should feel free to select either surgery or radiotherapy on the basis of the treatments’ QOL profiles, since the mortality profiles are equivalent.
Anthony V. D’Amico, MD, is in the department of radiation oncology at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, both in Boston. He reported having no relevant financial disclosures. Dr. D’Amico made these remarks in an editorial accompanying the two reports on the Protect trial (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEHMe1610395).
The three main approaches for treating localized prostate cancer – surgery, radiotherapy, or active monitoring – yield similar efficacy outcomes but different quality-of-life outcomes, according to two reports published on the New England Journal of Medicine.
Both reports present the findings of the ongoing Protect (Prostate Testing for Cancer and Treatment) trial, a large prospective, randomized trial in the United Kingdom comparing mortality and other health outcomes in men with PSA-detected localized disease. The trial involved 82,429 men aged 50-69 years who had a PSA test between 1999 and 2009, of whom 2,664 were found to have localized prostate cancer. A total of 1,643 of these participants agreed to be randomly assigned to radical prostatectomy (553 men), radical radiotherapy (545 men), or active monitoring (545 men).
“Active monitoring” involved avoiding any immediate therapy and regularly monitoring disease progression so that radical treatment with curative intent could be given if the need arose. Patients were monitored every 3 months for the first year, then every 6-12 months thereafter. This differs from “watchful waiting,” which doesn’t involve any plan for curative radical treatment if disease progresses.
The first report focused on mortality and disease progression in these 1,643 participants at a median of 10 years of follow-up. The primary outcome measure, prostate cancer–specific survival, was 98.8% or greater across all three study groups, and there was no significant difference among them. Thus, all three approaches yielded the same efficacy: prostate cancer–specific mortality of approximately 1%, said Freddie C. Hamdy, MD, of the Nuffield Department of Surgical Sciences, University of Oxford, and his associates.
However, the rate of disease progression among men assigned to surgery (8.9/1,000 person-years) or to radiotherapy (9.0/1,000 person-years) was less than half the rate among men assigned to active monitoring (22.9/1,000 person-years). The rate of metastasis followed this same pattern (2.4, 3.0, and 6.3 per 1,000 person-years, respectively).
“These differences show the effectiveness of immediate radical therapy over active monitoring, but they have not translated into significant differences – nor have they ruled out equivalence – in disease-specific or all-cause mortality; thus, longer-term follow-up is necessary,” Dr. Hamdy and his associates said (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606220).
The trade-off was that 44% of the men assigned to active monitoring were able to forgo both radical surgery and radical radiotherapy, avoiding the adverse effects of those treatments. These included nine thromboembolic or cardiovascular events, 14 transfusions, one rectal injury, and nine anastomotic problems requiring intervention, they noted.
It is important to remember that approximately one-fourth of the men assigned to active monitoring went on to undergo radical treatment within 3 years, and that more than half did so by the 10-year follow-up date, the investigators added.
The second report focused on patient-reported outcomes concerning urinary, bowel, sexual, and quality-of-life issues in the 1,643 participants at 6 years of follow-up. These differed markedly among the three study groups, said Jenny L. Donovan, PhD, of the School of Social and Community Medicine, University of Bristol, U.K., and her associates.
Prostatectomy had a clear negative effect on urinary continence and sexual function, particularly erectile function, compared with radiotherapy and active monitoring. This peaked at 6 months after surgery, and though some patients recovered some function over time, urinary incontinence remained worse in the prostatectomy group than in the other two groups throughout follow-up. The use of absorbent pads rose from 1% at baseline to 46% at 6 months in the prostatectomy group. In comparison, the 6-month rate in the radiotherapy group rose to only 5% and that in the active-monitoring group to only 4%.
Radiotherapy plus neoadjuvant androgen-deprivation therapy had more of a negative effect on bowel function, urinary voiding, and nocturia than did the other two treatment approaches. However, many patients eventually showed considerable recovery on most of these measures, except that they continued to have bloody stools more frequently than did men who had prostatectomy or active monitoring.
Men in the active-monitoring group had substantially less difficulty with urinary, sexual, and bowel function, as expected. However, this gradually worsened over time as increasing numbers of these men eventually underwent radical treatments, Dr. Donovan and her associates wrote (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606221).
Quality-of-life measures generally reflected these differences among the three study groups, “with some evidence of accommodation to changes over time.” General mental and physical health, cancer-specific quality of life, and anxiety and depression all were similar across the three groups at 6 years.
“Follow-up for an additional 5-10 years is required to fully inform decisions involving the trade-off between the shorter-term effects of the management strategies shown here and the longer course of progression and treatment of prostate cancer in the context of other life-threatening conditions,” they said.
The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.
The three main approaches for treating localized prostate cancer – surgery, radiotherapy, or active monitoring – yield similar efficacy outcomes but different quality-of-life outcomes, according to two reports published on the New England Journal of Medicine.
Both reports present the findings of the ongoing Protect (Prostate Testing for Cancer and Treatment) trial, a large prospective, randomized trial in the United Kingdom comparing mortality and other health outcomes in men with PSA-detected localized disease. The trial involved 82,429 men aged 50-69 years who had a PSA test between 1999 and 2009, of whom 2,664 were found to have localized prostate cancer. A total of 1,643 of these participants agreed to be randomly assigned to radical prostatectomy (553 men), radical radiotherapy (545 men), or active monitoring (545 men).
“Active monitoring” involved avoiding any immediate therapy and regularly monitoring disease progression so that radical treatment with curative intent could be given if the need arose. Patients were monitored every 3 months for the first year, then every 6-12 months thereafter. This differs from “watchful waiting,” which doesn’t involve any plan for curative radical treatment if disease progresses.
The first report focused on mortality and disease progression in these 1,643 participants at a median of 10 years of follow-up. The primary outcome measure, prostate cancer–specific survival, was 98.8% or greater across all three study groups, and there was no significant difference among them. Thus, all three approaches yielded the same efficacy: prostate cancer–specific mortality of approximately 1%, said Freddie C. Hamdy, MD, of the Nuffield Department of Surgical Sciences, University of Oxford, and his associates.
However, the rate of disease progression among men assigned to surgery (8.9/1,000 person-years) or to radiotherapy (9.0/1,000 person-years) was less than half the rate among men assigned to active monitoring (22.9/1,000 person-years). The rate of metastasis followed this same pattern (2.4, 3.0, and 6.3 per 1,000 person-years, respectively).
“These differences show the effectiveness of immediate radical therapy over active monitoring, but they have not translated into significant differences – nor have they ruled out equivalence – in disease-specific or all-cause mortality; thus, longer-term follow-up is necessary,” Dr. Hamdy and his associates said (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606220).
The trade-off was that 44% of the men assigned to active monitoring were able to forgo both radical surgery and radical radiotherapy, avoiding the adverse effects of those treatments. These included nine thromboembolic or cardiovascular events, 14 transfusions, one rectal injury, and nine anastomotic problems requiring intervention, they noted.
It is important to remember that approximately one-fourth of the men assigned to active monitoring went on to undergo radical treatment within 3 years, and that more than half did so by the 10-year follow-up date, the investigators added.
The second report focused on patient-reported outcomes concerning urinary, bowel, sexual, and quality-of-life issues in the 1,643 participants at 6 years of follow-up. These differed markedly among the three study groups, said Jenny L. Donovan, PhD, of the School of Social and Community Medicine, University of Bristol, U.K., and her associates.
Prostatectomy had a clear negative effect on urinary continence and sexual function, particularly erectile function, compared with radiotherapy and active monitoring. This peaked at 6 months after surgery, and though some patients recovered some function over time, urinary incontinence remained worse in the prostatectomy group than in the other two groups throughout follow-up. The use of absorbent pads rose from 1% at baseline to 46% at 6 months in the prostatectomy group. In comparison, the 6-month rate in the radiotherapy group rose to only 5% and that in the active-monitoring group to only 4%.
Radiotherapy plus neoadjuvant androgen-deprivation therapy had more of a negative effect on bowel function, urinary voiding, and nocturia than did the other two treatment approaches. However, many patients eventually showed considerable recovery on most of these measures, except that they continued to have bloody stools more frequently than did men who had prostatectomy or active monitoring.
Men in the active-monitoring group had substantially less difficulty with urinary, sexual, and bowel function, as expected. However, this gradually worsened over time as increasing numbers of these men eventually underwent radical treatments, Dr. Donovan and her associates wrote (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606221).
Quality-of-life measures generally reflected these differences among the three study groups, “with some evidence of accommodation to changes over time.” General mental and physical health, cancer-specific quality of life, and anxiety and depression all were similar across the three groups at 6 years.
“Follow-up for an additional 5-10 years is required to fully inform decisions involving the trade-off between the shorter-term effects of the management strategies shown here and the longer course of progression and treatment of prostate cancer in the context of other life-threatening conditions,” they said.
The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: The three main approaches for treating localized prostate cancer yield similar efficacy outcomes but different quality-of-life outcomes.
Major finding: All three treatment approaches – surgery, radiotherapy, and active monitoring – yielded the same efficacy: 10-year prostate cancer–specific mortality of approximately 1%.
Data source: The Protect trial, a prospective randomized study involving 1,643 prostate cancer patients in the U.K. followed for 10 years.
Disclosures: The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.
No link between vasectomy, prostate cancer in U.S. cohort
Vasectomy does not appear to be associated with prostate cancer mortality or prostate cancer incidence, according to findings from a large U.S. prospective cohort of men aged 40 years or older.
Prostate cancer mortality was examined in the overall Cancer Prevention Study II (CPS-II) cohort of 363,726 men, including 7,451 who died as a result of prostate cancer between 1982 and 2012, and no association was found with vasectomy (hazard ratio, 1.01).
Overall and high-grade prostate cancer incidence rates were examined among 66,542 men from the CPS-II Nutrition cohort subgroup, including 9,133 who were diagnosed with prostate cancer between 1991 and 2011, and again no associations were found with vasectomy (HR, 1.02 and 0.91, respectively), Eric J. Jacobs, PhD, and his colleagues at the American Cancer Society report (J Clin Oncol. 2016 Sep 19. doi: 10.1200/JCO.2015.66.2361).
Results were similar after adjusting for years since vasectomy and in analyses restricted to men aged 50 years and older, the investigators noted.
Findings from prior, smaller studies have been conflicting, but the current study – the largest-known study to date to examine the association between vasectomy and prostate cancer, according to the authors – provides “some reassurance that vasectomy is unlikely to meaningfully increase risk of prostate cancer,” they wrote.
The authors reported having no disclosures.
Vasectomy does not appear to be associated with prostate cancer mortality or prostate cancer incidence, according to findings from a large U.S. prospective cohort of men aged 40 years or older.
Prostate cancer mortality was examined in the overall Cancer Prevention Study II (CPS-II) cohort of 363,726 men, including 7,451 who died as a result of prostate cancer between 1982 and 2012, and no association was found with vasectomy (hazard ratio, 1.01).
Overall and high-grade prostate cancer incidence rates were examined among 66,542 men from the CPS-II Nutrition cohort subgroup, including 9,133 who were diagnosed with prostate cancer between 1991 and 2011, and again no associations were found with vasectomy (HR, 1.02 and 0.91, respectively), Eric J. Jacobs, PhD, and his colleagues at the American Cancer Society report (J Clin Oncol. 2016 Sep 19. doi: 10.1200/JCO.2015.66.2361).
Results were similar after adjusting for years since vasectomy and in analyses restricted to men aged 50 years and older, the investigators noted.
Findings from prior, smaller studies have been conflicting, but the current study – the largest-known study to date to examine the association between vasectomy and prostate cancer, according to the authors – provides “some reassurance that vasectomy is unlikely to meaningfully increase risk of prostate cancer,” they wrote.
The authors reported having no disclosures.
Vasectomy does not appear to be associated with prostate cancer mortality or prostate cancer incidence, according to findings from a large U.S. prospective cohort of men aged 40 years or older.
Prostate cancer mortality was examined in the overall Cancer Prevention Study II (CPS-II) cohort of 363,726 men, including 7,451 who died as a result of prostate cancer between 1982 and 2012, and no association was found with vasectomy (hazard ratio, 1.01).
Overall and high-grade prostate cancer incidence rates were examined among 66,542 men from the CPS-II Nutrition cohort subgroup, including 9,133 who were diagnosed with prostate cancer between 1991 and 2011, and again no associations were found with vasectomy (HR, 1.02 and 0.91, respectively), Eric J. Jacobs, PhD, and his colleagues at the American Cancer Society report (J Clin Oncol. 2016 Sep 19. doi: 10.1200/JCO.2015.66.2361).
Results were similar after adjusting for years since vasectomy and in analyses restricted to men aged 50 years and older, the investigators noted.
Findings from prior, smaller studies have been conflicting, but the current study – the largest-known study to date to examine the association between vasectomy and prostate cancer, according to the authors – provides “some reassurance that vasectomy is unlikely to meaningfully increase risk of prostate cancer,” they wrote.
The authors reported having no disclosures.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Vasectomy does not appear to be associated with prostate cancer mortality or prostate cancer incidence, according to findings from a large U.S. prospective cohort of men aged 40 years or older.
Major finding: No association between vasectomy and prostate cancer mortality (HR, 1.01), or between vasectomy and overall and high-grade prostate cancer incidence (HR, 1.02 and 0.91, respectively).
Data source: The prospective CPS II cohort (363,726 men) and CPS-II Nutrition Cohort (66,542 men).
Disclosures: The authors reported having no disclosures.
FDA modifies dosage regimen for nivolumab
The Food and Drug Administration has modified the dosage regimen for nivolumab for indications of renal cell carcinoma, metastatic melanoma, and non–small cell lung cancer.
The single-dose regimen of nivolumab (3 mg/kg IV every 2 weeks) is replaced with the new recommended regimen of 240 mg IV every 2 weeks until disease progression or intolerable toxicity, the FDA said in a written statement.
The nivolumab (Opdivo) dosing regimen in combination with ipilimumab for melanoma will stay the same (nivolumab 1 mg/kg IV, followed by ipilimumab on the same day, every 3 weeks for four doses); however, after completion of ipilimumab, the recommended nivolumab dose is modified to 240 mg every 2 weeks until disease progression or intolerable toxicity. The recommended dose for classical Hodgkin lymphoma remains at 3 mg/kg IV every 2 weeks until disease progression or intolerable toxicity.
The change was made based on analyses demonstrating the comparability of the pharmacokinetics exposure, safety, and efficacy of the proposed new dosing regimen with the previously approved regimen. “Based on simulations by the population pharmacokinetics model, [the] FDA determined that the overall exposure at 240 mg every 2 weeks flat dose is similar (less than 6% difference) to 3 mg/kg every 2 weeks. These differences in exposure are not likely to have a clinically meaningful effect on safety and efficacy, since dose/exposure response relationships appear to be relatively flat in these three indications,” the FDA said.
The Food and Drug Administration has modified the dosage regimen for nivolumab for indications of renal cell carcinoma, metastatic melanoma, and non–small cell lung cancer.
The single-dose regimen of nivolumab (3 mg/kg IV every 2 weeks) is replaced with the new recommended regimen of 240 mg IV every 2 weeks until disease progression or intolerable toxicity, the FDA said in a written statement.
The nivolumab (Opdivo) dosing regimen in combination with ipilimumab for melanoma will stay the same (nivolumab 1 mg/kg IV, followed by ipilimumab on the same day, every 3 weeks for four doses); however, after completion of ipilimumab, the recommended nivolumab dose is modified to 240 mg every 2 weeks until disease progression or intolerable toxicity. The recommended dose for classical Hodgkin lymphoma remains at 3 mg/kg IV every 2 weeks until disease progression or intolerable toxicity.
The change was made based on analyses demonstrating the comparability of the pharmacokinetics exposure, safety, and efficacy of the proposed new dosing regimen with the previously approved regimen. “Based on simulations by the population pharmacokinetics model, [the] FDA determined that the overall exposure at 240 mg every 2 weeks flat dose is similar (less than 6% difference) to 3 mg/kg every 2 weeks. These differences in exposure are not likely to have a clinically meaningful effect on safety and efficacy, since dose/exposure response relationships appear to be relatively flat in these three indications,” the FDA said.
The Food and Drug Administration has modified the dosage regimen for nivolumab for indications of renal cell carcinoma, metastatic melanoma, and non–small cell lung cancer.
The single-dose regimen of nivolumab (3 mg/kg IV every 2 weeks) is replaced with the new recommended regimen of 240 mg IV every 2 weeks until disease progression or intolerable toxicity, the FDA said in a written statement.
The nivolumab (Opdivo) dosing regimen in combination with ipilimumab for melanoma will stay the same (nivolumab 1 mg/kg IV, followed by ipilimumab on the same day, every 3 weeks for four doses); however, after completion of ipilimumab, the recommended nivolumab dose is modified to 240 mg every 2 weeks until disease progression or intolerable toxicity. The recommended dose for classical Hodgkin lymphoma remains at 3 mg/kg IV every 2 weeks until disease progression or intolerable toxicity.
The change was made based on analyses demonstrating the comparability of the pharmacokinetics exposure, safety, and efficacy of the proposed new dosing regimen with the previously approved regimen. “Based on simulations by the population pharmacokinetics model, [the] FDA determined that the overall exposure at 240 mg every 2 weeks flat dose is similar (less than 6% difference) to 3 mg/kg every 2 weeks. These differences in exposure are not likely to have a clinically meaningful effect on safety and efficacy, since dose/exposure response relationships appear to be relatively flat in these three indications,” the FDA said.
