Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): Results of phase III PREVAIL study.

Abstract

LBA1^ Background: Enzalutamide, an orally administered androgen receptor inhibitor, improved overall survival (OS) in men with mCRPC who had received prior docetaxel therapy (Scher et al, NEJM 367:13, 2012). This study examined whether enzalutamide could prolong OS and radiographic progression-free survival (rPFS) in asymptomatic or mildly symptomatic chemotherapy-naive men with mCRPC. Methods: In this randomized, double-blind, placebo-controlled, multinational phase 3 study (NCT01212991), chemotherapy-naive patients with mCRPC were stratified by site and randomized 1:1 to enzalutamide 160 mg/day or placebo. OS and rPFS were co-primary endpoints and analyzed for the intent-to-treat population. Planned sample size was 1,680 with 765 deaths to achieve 80% power to detect a target OS hazard ratio (HR) of 0.815 with a type I error rate of 0.049 and a single interim analysis at 516 (67%) deaths. The co-primary endpoint of rPFS had sufficient power to detect a target HR of 0.57 and a type I error rate of 0.001 with a minimum of 410 events. Results: A total of 1,717 men were randomized (1,715 treated) between September 2010 and September 2012. The interim analysis at 539 deaths showed a statistically significant benefit of enzalutamide over placebo with a 30% reduction in risk of death (OS: HR 0.70; 95% CI: 0.59-0.83; P< 0.0001) and an 81% reduction in risk of radiographic progression or death (rPFS: HR 0.19; 95% CI: 0.15-0.23; P< 0.0001). At the time of the analysis, 28% of enzalutamide patients and 35% of placebo patients had died. Estimated median OS was 32.4 months (mo) (95% CI, 31.5–upper limit not yet reached [NYR]) in the enzalutamide arm vs 30.2 mo (95% CI, 28–upper limit NYR) in the placebo arm. Median rPFS was NYR (95% CI: 13.8–upper limit NYR) in the enzalutamide arm vs 3.9 mo (95% CI: 3.7-5.4) in the placebo arm. Seizure events were reported in two patients. The Independent Data Monitoring Committee considered the benefit-risk ratio to favor enzalutamide and recommended stopping the study and crossing placebo patients to enzalutamide. Secondary endpoints and safety analysis will be presented. Conclusions: Treatment with enzalutamide significantly improves OS and rPFS in men with chemotherapy-naive mCRPC. Clinical trial information: NCT01212991.