Enzalutamide Improves Overall Survival in Biochemical Recurrence

Key Takeaways

• Combination therapy was associated with longer overall survival than leuprolide alone in the final analysis.
• Enzalutamide monotherapy was not significantly different from leuprolide alone for overall survival.
• Descriptive updates for prespecified secondary end points were similar to prior reporting, and safety findings were consistent with the primary analysis.

In the final analysis, 8-year overall survival was 78.9% with the combination and 69.5% with leuprolide alone. The report adds the prespecified overall survival readout to a study previously defined by metastasis-free survival findings in the same population. Enzalutamide monotherapy remained in the three-arm comparison but did not significantly differ from leuprolide alone for overall survival. In this analysis, the overall survival advantage was observed with combination therapy rather than monotherapy.

EMBARK was a randomized phase 3 trial in patients with prostate cancer and high-risk biochemical recurrence after prior local therapy. Participants were assigned in a 1:1:1 ratio to enzalutamide plus leuprolide, leuprolide alone, or enzalutamide monotherapy. The primary end point was metastasis-free survival, assessed in the combination group against the leuprolide-alone group for the primary comparison. Overall survival was an alpha-controlled key secondary end point within the prespecified hierarchy of outcomes. This analysis provides the planned overall survival update within that sequence.

In the final overall survival analysis, the hazard ratio for death with enzalutamide plus leuprolide versus leuprolide alone was 0.60. The 95% confidence interval was 0.44 to 0.80, and the comparison met statistical significance with P<0.001. For enzalutamide monotherapy, 8-year overall survival was 73.1% compared with the leuprolide-alone group over the reported time frame. Its hazard ratio for death was 0.83, with a 95% confidence interval of 0.63 to 1.10 versus leuprolide alone. The monotherapy comparison had P=0.19, so only the combination arm showed a statistically significant overall survival difference versus leuprolide alone.

Prespecified secondary end points included time to first use of new antineoplastic therapy and time to first symptomatic skeletal event. Progression-free survival with first subsequent therapy was identified as an exploratory end point. Descriptive updates for the prespecified secondary end points were similar to those presented previously in the trial. Safety findings were consistent with the primary metastasis-free survival analysis. EMBARK is registered under NCT02319837, and Pfizer and Astellas Pharma funded the trial.