Enzalutamide Monotherapy Shows Higher Survival and Metastasis-Free Rates Versus Leuprolide in High-Risk Biochemical Recurrence

PURPOSE: Primary analysis of the phase 3 EMBARK trial reported efficacy and safety outcomes for enzalutamide monotherapy in patients with high-risk biochemical recurrence. Here, we report secondary end points for enzalutamide monotherapy vs leuprolide alone. MATERIALS AND METHODS: Patients were randomized (1:1:1) to enzalutamide plus leuprolide, leuprolide alone, or enzalutamide monotherapy. Overall survival was a key secondary end point; non-key secondary end points were time to: distant metastasis, symptomatic progression, first symptomatic skeletal event, and resumption of any hormonal therapy. Sexual health was assessed using the Quality of Life Questionnaire-Prostate 25. Time-to-event end points were summarized using Kaplan-Meier methods with nominal values. RESULTS: Five-year probability rates (95% CI) for enzalutamide monotherapy vs leuprolide alone were: overall survival, 89.5% (85.6-92.4) vs 87.2% (83.0-90.4); time to remaining free from distant metastasis, 86.8% (82.3-90.2) vs 81.5% (76.3-85.7); symptomatic progression, 66.6% (61.2-71.4) vs 53.3% (47.6-58.6); and first symptomatic skeletal event, 95.8% (92.9-97.6) vs 91.5% (87.8-94.1). After treatment suspension, the 5-year probability rate (95% CI) of remaining free from resumption of any hormonal therapy for leuprolide alone vs enzalutamide monotherapy was 7.8% (4.4-12.3) vs 5.6% (3.3-8.8). Sexual health was better preserved in patients treated with enzalutamide monotherapy than leuprolide alone (HR 0.76; 95% CI: 0.62-0.94; = .008). After discontinuation, most patients were subsequently treated with hormonal therapies in both groups. CONCLUSIONS: Secondary end point results support enzalutamide monotherapy as a potential option to improve efficacy and preserve sexual health vs leuprolide alone for patients with high-risk biochemical recurrence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02319837.