Improved Survival with Enzalutamide in Biochemically Recurrent Prostate Cancer.

[BACKGROUND] In the phase 3 EMBARK trial, enzalutamide plus leuprolide and enzalutamide monotherapy were associated with longer metastasis-free survival than leuprolide alone among patients with biochemically recurrent prostate cancer. The final analysis of overall survival has not been reported.

[METHODS] We randomly assigned patients with prostate cancer who had high-risk biochemical recurrence in a 1:1:1 ratio to receive enzalutamide plus leuprolide (the combination group), leuprolide alone (the leuprolide-alone group), or enzalutamide monotherapy (the monotherapy group). The primary end point was metastasis-free survival, assessed in the combination group as compared with the leuprolide-alone group. Overall survival was an alpha-controlled, key secondary end point. Updated results for prespecified secondary end points, including the time to first use of new antineoplastic therapy and the time to the first symptomatic skeletal event, were summarized descriptively, as was progression-free survival with the first subsequent therapy, an exploratory end point.

[RESULTS] The 8-year overall survival was 78.9% (95% confidence interval [CI], 73.9 to 83.1) in the combination group and 69.5% (95% CI, 64.0 to 74.3) in the leuprolide-alone group; the hazard ratio for death was 0.60 (95% CI, 0.44 to 0.80; P<0.001). The 8-year overall survival with monotherapy was 73.1% (95% CI, 67.6 to 77.9), which did not differ significantly from that with leuprolide alone (hazard ratio, 0.83; 95% CI, 0.63 to 1.10; P = 0.19). In the descriptive updates for prespecified secondary end points, results were similar to those previously reported. Safety findings were consistent with those in the primary analysis of metastasis-free survival.

[CONCLUSIONS] Overall survival was significantly longer with the combination of enzalutamide and leuprolide than with leuprolide alone among patients with prostate cancer with high-risk biochemical recurrence. Enzalutamide monotherapy was not superior to leuprolide alone in the analysis of overall survival. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.).