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CHICAGO – The answer was nearly a decade in coming, but worth the wait: Adding docetaxel to initial hormonal therapy in men with metastatic, hormone-sensitive prostate cancer can extend overall survival by more than a year.
In a randomized phase III trial, median overall survival for men who received upfront androgen deprivation therapy (ADT) alone for 18 weeks was 44 months, compared with 57.6 months for men who received ADT plus docetaxel (Taxotere), reported Dr. Christopher Sweeney of the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute, Boston.
"The certainty of the data is strong for patients with a high volume of metastatic disease and clearly justifies the treatment burden. This is one of the biggest improvements in survival we have seen involving patients with an adult, node-metastatic solid tumor," said Dr. Sweeney, who presented the data at a media briefing and in a plenary session at the annual meeting of the American Society of Clinical Oncology.
"In prostate cancer, I’m not aware of an historical study that ever offered up quite this magnitude of improvement in survival," commented Dr. Clifford Hudis, who moderated the briefing and the plenary session.
Dr. Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan–Kettering Cancer Center in New York, was not involved in the study.
In this study of 790 men with newly diagnosed metastatic prostate cancer, those with more extensive disease at study entry (520 patients) experienced the greatest benefit from the docetaxel-ADT combination, with a median overall survival of 49.2 months, compared with 32.2 months for men with extensive disease who received ADT alone.
Median overall survival for men with less invasive disease, has not yet been reached, Dr. Sweeney noted.
Start docetaxel earlier?
The CHAARTED (Chemo Hormonal Therapy vs. Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) study began enrolling patients in 2006. Because there was evidence to show that docetaxel improves overall survival of men with metastatic prostate cancer who had disease progression while on ADT, the investigators wanted to see whether starting docetaxel earlier might provide additional benefit.
They randomly assigned men on a 1:1 basis to receive either ADT alone, or ADT plus docetaxel 75 mg/m2 every 3 weeks for six cycles within 4 months of starting ADT. Patients were stratified by low- vs. high volume disease, with high-volume defined as visceral metastases and/or four or more metastatic bone lesions; antiandrogen therapy use beyond 30 days, age, ECOG (Eastern Cooperative Oncology Group) performance status, prior adjuvant ADT for less than or more than 1 year, and whether they had used a Food and Drug Administration–approved drug for preventing skeletal events, such as a bisphosphonate.
Of the patients assigned to ADT only, 124 received docetaxel at the time of disease progression. Of those in the combination group, 45 who had disease progression received additional docetaxel.
Data released early
At the fourth planned interim analysis in September 2013, when 53% of planned information had been accrued, the data-monitoring committee determined that the ADT-docetaxel combination had crossed the O’Brien-Fleming upper boundary, signaling statistically significant efficacy, and decided to release all available data.
As of Jan. 16, 2014, with a median follow-up of 29 months, there had been 137 deaths among patients treated with ADT alone, compared with 104 treated with ADT-docetaxel.
As noted before, median overall survival was 44 months for those on ADT alone, compared with 57.6 months for those on the combination (P = .0006). This translated into a hazard ratio for death of 0.61 (P = .0003).
The hazard ratio was similar for the subset of men with high-volume disease, at 0.60 (P = .0006), who received both ADT and docetaxel. The hazard ratio for men with low-volume disease was not significant, but as noted before, median overall survival in this group has not yet been reached, likely because men with low-volume disease tend to derive greater benefit from ADT, suggesting that it may take longer follow-up for an added effect of docetaxel to be seen.
In addition to the survival advantage, the combination was better than ADT alone at driving down prostate-specific antigen (PSA) levels, with 27.5% of patients on the ADT-docetaxel arm having a PSA below 0.2 ng/mL at 6 months, compared with 14% of patients treated with ADT alone (P less than .0001). At 12 months, the respective percentages were 22.7% and 11.7% (P less than .0001)
The combination was also better at delaying the median time to development of castration-resistant prostate cancer (20.7 vs. 14.7 months; P less than .0001), and the median time to clinical progression (32.7 vs. 19.8 months).
The most serious adverse events were febrile neutropenia and neuropathy. Of the 101 patients in the combination group who died, 84 of the deaths (83.2%) were from prostate cancer, 8 were from unknown causes, and 1 was attributed to the study protocol. Of the 136 in the ADT-alone arm who died, 112 deaths (83.6%) were from prostate cancers, and 22 were from other or unknown causes; data on the causes of death in 2 patients were missing.
"The clinical interpretation of the data is that six cycles of docetaxel in addition to ADT represents an appropriate option for men with metastatic prostate cancer commencing ADT who are suitable for docetaxel therapy," Dr. Sweeney said in the plenary session.
Dr. Michael J, Morris, the invited discussant, pointed out that the superior overall survival seen with the combination in this study far outstrips that of other drugs tried in this population, with median overall survival benefits ranging from 2.2 to 5.2 months.
"The investigators have adequately shown that high-volume patients with castration-sensitive metastatic disease can benefit from upfront docetaxel," he said. "But there is insufficient data at this after 29 months of median follow-up to recommend that low-volume patients with castration-sensitive disease undergo chemotherapy. We need to optimize the distinction between those who benefit from chemotherapy and those who don’t."
Dr. Morris of Memorial Sloan–Kettering Cancer Center and of Weill Cornell Medical College in New York was not involved in the study.
The study was funded by the National Cancer Institute. Dr. Sweeney disclosed serving in a consulting or advisory role to Astellas Pharma, BIND Biosciences; Bionomics, Exelixis, Genentech, Janssen Pharmaceuticals, Roche and Sanofi. Dr. Morris disclosed consulting/advising Astellas, Bayer, Janssen, Millennium, and Progenics, stock ownership in Biogen Idec, Procter & Gamble, and Teva, and research funding from Agensys, Algeta, Bayer, Medivation, and Sanofi. Dr. Hudis served as a DSMB Chair for Genentech and received research grants from Onyx Pharmaceuticals and Merck & Co.
CHICAGO – The answer was nearly a decade in coming, but worth the wait: Adding docetaxel to initial hormonal therapy in men with metastatic, hormone-sensitive prostate cancer can extend overall survival by more than a year.
In a randomized phase III trial, median overall survival for men who received upfront androgen deprivation therapy (ADT) alone for 18 weeks was 44 months, compared with 57.6 months for men who received ADT plus docetaxel (Taxotere), reported Dr. Christopher Sweeney of the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute, Boston.
"The certainty of the data is strong for patients with a high volume of metastatic disease and clearly justifies the treatment burden. This is one of the biggest improvements in survival we have seen involving patients with an adult, node-metastatic solid tumor," said Dr. Sweeney, who presented the data at a media briefing and in a plenary session at the annual meeting of the American Society of Clinical Oncology.
"In prostate cancer, I’m not aware of an historical study that ever offered up quite this magnitude of improvement in survival," commented Dr. Clifford Hudis, who moderated the briefing and the plenary session.
Dr. Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan–Kettering Cancer Center in New York, was not involved in the study.
In this study of 790 men with newly diagnosed metastatic prostate cancer, those with more extensive disease at study entry (520 patients) experienced the greatest benefit from the docetaxel-ADT combination, with a median overall survival of 49.2 months, compared with 32.2 months for men with extensive disease who received ADT alone.
Median overall survival for men with less invasive disease, has not yet been reached, Dr. Sweeney noted.
Start docetaxel earlier?
The CHAARTED (Chemo Hormonal Therapy vs. Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) study began enrolling patients in 2006. Because there was evidence to show that docetaxel improves overall survival of men with metastatic prostate cancer who had disease progression while on ADT, the investigators wanted to see whether starting docetaxel earlier might provide additional benefit.
They randomly assigned men on a 1:1 basis to receive either ADT alone, or ADT plus docetaxel 75 mg/m2 every 3 weeks for six cycles within 4 months of starting ADT. Patients were stratified by low- vs. high volume disease, with high-volume defined as visceral metastases and/or four or more metastatic bone lesions; antiandrogen therapy use beyond 30 days, age, ECOG (Eastern Cooperative Oncology Group) performance status, prior adjuvant ADT for less than or more than 1 year, and whether they had used a Food and Drug Administration–approved drug for preventing skeletal events, such as a bisphosphonate.
Of the patients assigned to ADT only, 124 received docetaxel at the time of disease progression. Of those in the combination group, 45 who had disease progression received additional docetaxel.
Data released early
At the fourth planned interim analysis in September 2013, when 53% of planned information had been accrued, the data-monitoring committee determined that the ADT-docetaxel combination had crossed the O’Brien-Fleming upper boundary, signaling statistically significant efficacy, and decided to release all available data.
As of Jan. 16, 2014, with a median follow-up of 29 months, there had been 137 deaths among patients treated with ADT alone, compared with 104 treated with ADT-docetaxel.
As noted before, median overall survival was 44 months for those on ADT alone, compared with 57.6 months for those on the combination (P = .0006). This translated into a hazard ratio for death of 0.61 (P = .0003).
The hazard ratio was similar for the subset of men with high-volume disease, at 0.60 (P = .0006), who received both ADT and docetaxel. The hazard ratio for men with low-volume disease was not significant, but as noted before, median overall survival in this group has not yet been reached, likely because men with low-volume disease tend to derive greater benefit from ADT, suggesting that it may take longer follow-up for an added effect of docetaxel to be seen.
In addition to the survival advantage, the combination was better than ADT alone at driving down prostate-specific antigen (PSA) levels, with 27.5% of patients on the ADT-docetaxel arm having a PSA below 0.2 ng/mL at 6 months, compared with 14% of patients treated with ADT alone (P less than .0001). At 12 months, the respective percentages were 22.7% and 11.7% (P less than .0001)
The combination was also better at delaying the median time to development of castration-resistant prostate cancer (20.7 vs. 14.7 months; P less than .0001), and the median time to clinical progression (32.7 vs. 19.8 months).
The most serious adverse events were febrile neutropenia and neuropathy. Of the 101 patients in the combination group who died, 84 of the deaths (83.2%) were from prostate cancer, 8 were from unknown causes, and 1 was attributed to the study protocol. Of the 136 in the ADT-alone arm who died, 112 deaths (83.6%) were from prostate cancers, and 22 were from other or unknown causes; data on the causes of death in 2 patients were missing.
"The clinical interpretation of the data is that six cycles of docetaxel in addition to ADT represents an appropriate option for men with metastatic prostate cancer commencing ADT who are suitable for docetaxel therapy," Dr. Sweeney said in the plenary session.
Dr. Michael J, Morris, the invited discussant, pointed out that the superior overall survival seen with the combination in this study far outstrips that of other drugs tried in this population, with median overall survival benefits ranging from 2.2 to 5.2 months.
"The investigators have adequately shown that high-volume patients with castration-sensitive metastatic disease can benefit from upfront docetaxel," he said. "But there is insufficient data at this after 29 months of median follow-up to recommend that low-volume patients with castration-sensitive disease undergo chemotherapy. We need to optimize the distinction between those who benefit from chemotherapy and those who don’t."
Dr. Morris of Memorial Sloan–Kettering Cancer Center and of Weill Cornell Medical College in New York was not involved in the study.
The study was funded by the National Cancer Institute. Dr. Sweeney disclosed serving in a consulting or advisory role to Astellas Pharma, BIND Biosciences; Bionomics, Exelixis, Genentech, Janssen Pharmaceuticals, Roche and Sanofi. Dr. Morris disclosed consulting/advising Astellas, Bayer, Janssen, Millennium, and Progenics, stock ownership in Biogen Idec, Procter & Gamble, and Teva, and research funding from Agensys, Algeta, Bayer, Medivation, and Sanofi. Dr. Hudis served as a DSMB Chair for Genentech and received research grants from Onyx Pharmaceuticals and Merck & Co.
CHICAGO – The answer was nearly a decade in coming, but worth the wait: Adding docetaxel to initial hormonal therapy in men with metastatic, hormone-sensitive prostate cancer can extend overall survival by more than a year.
In a randomized phase III trial, median overall survival for men who received upfront androgen deprivation therapy (ADT) alone for 18 weeks was 44 months, compared with 57.6 months for men who received ADT plus docetaxel (Taxotere), reported Dr. Christopher Sweeney of the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute, Boston.
"The certainty of the data is strong for patients with a high volume of metastatic disease and clearly justifies the treatment burden. This is one of the biggest improvements in survival we have seen involving patients with an adult, node-metastatic solid tumor," said Dr. Sweeney, who presented the data at a media briefing and in a plenary session at the annual meeting of the American Society of Clinical Oncology.
"In prostate cancer, I’m not aware of an historical study that ever offered up quite this magnitude of improvement in survival," commented Dr. Clifford Hudis, who moderated the briefing and the plenary session.
Dr. Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan–Kettering Cancer Center in New York, was not involved in the study.
In this study of 790 men with newly diagnosed metastatic prostate cancer, those with more extensive disease at study entry (520 patients) experienced the greatest benefit from the docetaxel-ADT combination, with a median overall survival of 49.2 months, compared with 32.2 months for men with extensive disease who received ADT alone.
Median overall survival for men with less invasive disease, has not yet been reached, Dr. Sweeney noted.
Start docetaxel earlier?
The CHAARTED (Chemo Hormonal Therapy vs. Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) study began enrolling patients in 2006. Because there was evidence to show that docetaxel improves overall survival of men with metastatic prostate cancer who had disease progression while on ADT, the investigators wanted to see whether starting docetaxel earlier might provide additional benefit.
They randomly assigned men on a 1:1 basis to receive either ADT alone, or ADT plus docetaxel 75 mg/m2 every 3 weeks for six cycles within 4 months of starting ADT. Patients were stratified by low- vs. high volume disease, with high-volume defined as visceral metastases and/or four or more metastatic bone lesions; antiandrogen therapy use beyond 30 days, age, ECOG (Eastern Cooperative Oncology Group) performance status, prior adjuvant ADT for less than or more than 1 year, and whether they had used a Food and Drug Administration–approved drug for preventing skeletal events, such as a bisphosphonate.
Of the patients assigned to ADT only, 124 received docetaxel at the time of disease progression. Of those in the combination group, 45 who had disease progression received additional docetaxel.
Data released early
At the fourth planned interim analysis in September 2013, when 53% of planned information had been accrued, the data-monitoring committee determined that the ADT-docetaxel combination had crossed the O’Brien-Fleming upper boundary, signaling statistically significant efficacy, and decided to release all available data.
As of Jan. 16, 2014, with a median follow-up of 29 months, there had been 137 deaths among patients treated with ADT alone, compared with 104 treated with ADT-docetaxel.
As noted before, median overall survival was 44 months for those on ADT alone, compared with 57.6 months for those on the combination (P = .0006). This translated into a hazard ratio for death of 0.61 (P = .0003).
The hazard ratio was similar for the subset of men with high-volume disease, at 0.60 (P = .0006), who received both ADT and docetaxel. The hazard ratio for men with low-volume disease was not significant, but as noted before, median overall survival in this group has not yet been reached, likely because men with low-volume disease tend to derive greater benefit from ADT, suggesting that it may take longer follow-up for an added effect of docetaxel to be seen.
In addition to the survival advantage, the combination was better than ADT alone at driving down prostate-specific antigen (PSA) levels, with 27.5% of patients on the ADT-docetaxel arm having a PSA below 0.2 ng/mL at 6 months, compared with 14% of patients treated with ADT alone (P less than .0001). At 12 months, the respective percentages were 22.7% and 11.7% (P less than .0001)
The combination was also better at delaying the median time to development of castration-resistant prostate cancer (20.7 vs. 14.7 months; P less than .0001), and the median time to clinical progression (32.7 vs. 19.8 months).
The most serious adverse events were febrile neutropenia and neuropathy. Of the 101 patients in the combination group who died, 84 of the deaths (83.2%) were from prostate cancer, 8 were from unknown causes, and 1 was attributed to the study protocol. Of the 136 in the ADT-alone arm who died, 112 deaths (83.6%) were from prostate cancers, and 22 were from other or unknown causes; data on the causes of death in 2 patients were missing.
"The clinical interpretation of the data is that six cycles of docetaxel in addition to ADT represents an appropriate option for men with metastatic prostate cancer commencing ADT who are suitable for docetaxel therapy," Dr. Sweeney said in the plenary session.
Dr. Michael J, Morris, the invited discussant, pointed out that the superior overall survival seen with the combination in this study far outstrips that of other drugs tried in this population, with median overall survival benefits ranging from 2.2 to 5.2 months.
"The investigators have adequately shown that high-volume patients with castration-sensitive metastatic disease can benefit from upfront docetaxel," he said. "But there is insufficient data at this after 29 months of median follow-up to recommend that low-volume patients with castration-sensitive disease undergo chemotherapy. We need to optimize the distinction between those who benefit from chemotherapy and those who don’t."
Dr. Morris of Memorial Sloan–Kettering Cancer Center and of Weill Cornell Medical College in New York was not involved in the study.
The study was funded by the National Cancer Institute. Dr. Sweeney disclosed serving in a consulting or advisory role to Astellas Pharma, BIND Biosciences; Bionomics, Exelixis, Genentech, Janssen Pharmaceuticals, Roche and Sanofi. Dr. Morris disclosed consulting/advising Astellas, Bayer, Janssen, Millennium, and Progenics, stock ownership in Biogen Idec, Procter & Gamble, and Teva, and research funding from Agensys, Algeta, Bayer, Medivation, and Sanofi. Dr. Hudis served as a DSMB Chair for Genentech and received research grants from Onyx Pharmaceuticals and Merck & Co.
AT THE ASCO ANNUAL MEETING 2014
Key clinical finding: Adding docetaxel to hormonal therapy at the time of diagnosis of metastatic prostate cancer extends survival.
Major finding: Patients receiving docetaxel and androgen deprivation therapy at the time of diagnoses had median overall survival that was 13.6 months longer than men who received androgen deprivation therapy alone.
Data source: Randomized trial in 790 men with newly diagnosed metastatic hormone-sensitive prostate cancer.
Disclosures: The study was funded by the National Cancer Institute. Dr. Sweeney disclosed serving in a consulting or advisory role to Astellas Pharma, BIND Biosciences; Bionomics, Exelixis, Genentech, Janssen Pharmaceuticals, Roche, and Sanofi. Dr. Morris disclosed consulting/advising Astellas, Bayer, Janssen, Millennium, and Progenics, stock ownership in Biogen Idec, Procter & Gamble, and Teva, and research funding from Agensys, Algeta, Bayer, Medivation, and Sanofi. Dr. Hudis served as a DSMB Chair for Genentech and received research grants from Onyx Pharmaceuticals and Merck & Co.
