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For men with hormone-sensitive metastatic prostate cancer, combining standard androgen deprivation therapy with six cycles of docetaxel resulted in a significantly longer overall survival, compared with standard ADT alone, according to a study published online in the New England Journal of Medicine.
Men who received the combination therapy had “better cancer control than that with ADT alone, with a longer time to the development of castration resistance, a higher rate of decrease of the PSA level to less than 0.2 ng per milliliter at 12 months, a lower number of prostate-cancer deaths, and substantially longer overall survival,” wrote Dr. Christopher J. Sweeney of the Dana Farber Cancer Institute, Boston, and his colleagues (N Engl J Med. 2015 Aug 5. doi: 10.1056/NEJMoa1503747).
Investigators sought to find out whether docetaxel therapy given at the beginning of ADT for metastatic hormone-sensitive prostate cancer would result in a longer overall survival than with ADT alone, even though previous studies of chemotherapy plus ADT did not show a benefit. However, the researchers noted that these were small studies that primarily included patients with a relatively low tumor burden.
The study included 790 men with metastatic hormone sensitive prostate cancer, with a median age of 64 years (range, 36 to 88) in the combination group and 63 years (range, 39 to 91) in the ADT-alone group. In both groups, approximately 70% had an ECOG performance-status score of 0, 65% had high-volume disease, and 60% had a Gleason score of 8 or higher. In both cohorts, 73% had received no prior therapy with a curative intent.
The median overall survival was 13.6 months longer in the group receiving ADT and docetaxel, compared with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P less than.001).
There were 85 prostate cancer deaths in the combination therapy group, compared with 114 prostate cancer deaths in the ADT-alone group.
The addition of docetaxel to the regimen appeared to benefit all subgroups analyzed, although the median survival at the time of the analysis had not been reached in the subgroup with low-volume disease, in either of the two groups.
The “benefit at the last analysis was more apparent in the subgroup with high-volume disease than in the overall study population,” noted Dr. Sweeney and colleagues. Median overall survival was 17.0 months longer in the combination group than in the ADT-alone group (49.2 months vs.32.2 months; HR for death, 0.60; 95% CI, 0.45 to 0.81; P less than.001).
As for secondary endpoints, the proportion of patients who showed a decline in the PSA level to less than 0.2 ng/mL at 12 months was higher in the combination therapy group: 27.7% compared with 16.8% in the ADT-alone group (P less than.001).
The median time to the development of castration-resistant prostate cancer (biochemical, symptomatic, or radiographic) was also longer in the combination therapy group (20.2 months vs 11.7 months; HR 0.61; 95% CI, 0.51 to 0.72; P less than.001), as was median time to clinical progression (33.0 months vs 19.8 months, HR, 0.61; 95% CI, 0.50 to 0.75; P less than.001).
The addition of docetaxel was associated with higher toxicity. In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, grade 3 or 4 infection with neutropenia was 2.3%, and approximately 1% of the patients had a thromboembolic event.
For men with hormone-sensitive metastatic prostate cancer, combining standard androgen deprivation therapy with six cycles of docetaxel resulted in a significantly longer overall survival, compared with standard ADT alone, according to a study published online in the New England Journal of Medicine.
Men who received the combination therapy had “better cancer control than that with ADT alone, with a longer time to the development of castration resistance, a higher rate of decrease of the PSA level to less than 0.2 ng per milliliter at 12 months, a lower number of prostate-cancer deaths, and substantially longer overall survival,” wrote Dr. Christopher J. Sweeney of the Dana Farber Cancer Institute, Boston, and his colleagues (N Engl J Med. 2015 Aug 5. doi: 10.1056/NEJMoa1503747).
Investigators sought to find out whether docetaxel therapy given at the beginning of ADT for metastatic hormone-sensitive prostate cancer would result in a longer overall survival than with ADT alone, even though previous studies of chemotherapy plus ADT did not show a benefit. However, the researchers noted that these were small studies that primarily included patients with a relatively low tumor burden.
The study included 790 men with metastatic hormone sensitive prostate cancer, with a median age of 64 years (range, 36 to 88) in the combination group and 63 years (range, 39 to 91) in the ADT-alone group. In both groups, approximately 70% had an ECOG performance-status score of 0, 65% had high-volume disease, and 60% had a Gleason score of 8 or higher. In both cohorts, 73% had received no prior therapy with a curative intent.
The median overall survival was 13.6 months longer in the group receiving ADT and docetaxel, compared with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P less than.001).
There were 85 prostate cancer deaths in the combination therapy group, compared with 114 prostate cancer deaths in the ADT-alone group.
The addition of docetaxel to the regimen appeared to benefit all subgroups analyzed, although the median survival at the time of the analysis had not been reached in the subgroup with low-volume disease, in either of the two groups.
The “benefit at the last analysis was more apparent in the subgroup with high-volume disease than in the overall study population,” noted Dr. Sweeney and colleagues. Median overall survival was 17.0 months longer in the combination group than in the ADT-alone group (49.2 months vs.32.2 months; HR for death, 0.60; 95% CI, 0.45 to 0.81; P less than.001).
As for secondary endpoints, the proportion of patients who showed a decline in the PSA level to less than 0.2 ng/mL at 12 months was higher in the combination therapy group: 27.7% compared with 16.8% in the ADT-alone group (P less than.001).
The median time to the development of castration-resistant prostate cancer (biochemical, symptomatic, or radiographic) was also longer in the combination therapy group (20.2 months vs 11.7 months; HR 0.61; 95% CI, 0.51 to 0.72; P less than.001), as was median time to clinical progression (33.0 months vs 19.8 months, HR, 0.61; 95% CI, 0.50 to 0.75; P less than.001).
The addition of docetaxel was associated with higher toxicity. In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, grade 3 or 4 infection with neutropenia was 2.3%, and approximately 1% of the patients had a thromboembolic event.
For men with hormone-sensitive metastatic prostate cancer, combining standard androgen deprivation therapy with six cycles of docetaxel resulted in a significantly longer overall survival, compared with standard ADT alone, according to a study published online in the New England Journal of Medicine.
Men who received the combination therapy had “better cancer control than that with ADT alone, with a longer time to the development of castration resistance, a higher rate of decrease of the PSA level to less than 0.2 ng per milliliter at 12 months, a lower number of prostate-cancer deaths, and substantially longer overall survival,” wrote Dr. Christopher J. Sweeney of the Dana Farber Cancer Institute, Boston, and his colleagues (N Engl J Med. 2015 Aug 5. doi: 10.1056/NEJMoa1503747).
Investigators sought to find out whether docetaxel therapy given at the beginning of ADT for metastatic hormone-sensitive prostate cancer would result in a longer overall survival than with ADT alone, even though previous studies of chemotherapy plus ADT did not show a benefit. However, the researchers noted that these were small studies that primarily included patients with a relatively low tumor burden.
The study included 790 men with metastatic hormone sensitive prostate cancer, with a median age of 64 years (range, 36 to 88) in the combination group and 63 years (range, 39 to 91) in the ADT-alone group. In both groups, approximately 70% had an ECOG performance-status score of 0, 65% had high-volume disease, and 60% had a Gleason score of 8 or higher. In both cohorts, 73% had received no prior therapy with a curative intent.
The median overall survival was 13.6 months longer in the group receiving ADT and docetaxel, compared with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P less than.001).
There were 85 prostate cancer deaths in the combination therapy group, compared with 114 prostate cancer deaths in the ADT-alone group.
The addition of docetaxel to the regimen appeared to benefit all subgroups analyzed, although the median survival at the time of the analysis had not been reached in the subgroup with low-volume disease, in either of the two groups.
The “benefit at the last analysis was more apparent in the subgroup with high-volume disease than in the overall study population,” noted Dr. Sweeney and colleagues. Median overall survival was 17.0 months longer in the combination group than in the ADT-alone group (49.2 months vs.32.2 months; HR for death, 0.60; 95% CI, 0.45 to 0.81; P less than.001).
As for secondary endpoints, the proportion of patients who showed a decline in the PSA level to less than 0.2 ng/mL at 12 months was higher in the combination therapy group: 27.7% compared with 16.8% in the ADT-alone group (P less than.001).
The median time to the development of castration-resistant prostate cancer (biochemical, symptomatic, or radiographic) was also longer in the combination therapy group (20.2 months vs 11.7 months; HR 0.61; 95% CI, 0.51 to 0.72; P less than.001), as was median time to clinical progression (33.0 months vs 19.8 months, HR, 0.61; 95% CI, 0.50 to 0.75; P less than.001).
The addition of docetaxel was associated with higher toxicity. In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, grade 3 or 4 infection with neutropenia was 2.3%, and approximately 1% of the patients had a thromboembolic event.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Androgen deprivation therapy plus six cycles of docetaxel resulted in significantly longer overall survival compared with ADT alone in men with hormone-sensitive metastatic prostate cancer.
Major finding: Median overall survival was 13.6 months longer with ADT plus docetaxel than with ADT alone (57.6 months vs. 44.0 months; P less than .001).
Data source: Randomized controlled trial of 790 patients who received ADT combined with docetaxel or ADT alone.
Disclosures: The study was supported in part by the National Cancer Institute, National Institutes of Health, U.S. Department of Health & Human Services, and by the Public Health Service. Sanofi provided the docetaxel and a grant to ECOG-ACRIN. Several of the authors reported ties with industry.
