Background: The PREVAIL study examined the impact of enzalutamide on overall survival (OS) and radiographic progression-free survival (rPFS) in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients progressing despite androgen deprivation therapy.
Aim: Here we report primary outcomes from the full PREVAIL population and from the Australian/Asian cohort.
Methods: This, double-blind, placebo-controlled, multinational, Phase 3 study randomized patients 1:1 to enzalutamide 160 mg/day or placebo. OS and rPFS were co-primary endpoints. Planned sample size was 1680 (765 deaths) to achieve 80% power to detect a target OS hazard ratio (HR) of 0.815 with a 2-sided type I error rate of 0.049 and a single interim analysis at 516 (67%) deaths. The co-primary endpoint of rPFS had >99% power to detect a target HR of 0.57 and a 2-sided type I error rate of 0.001 with a minimum of 410 events. Pre-specified analyses of patients enrolled from Australia and Asia followed the same methodologies.
Results: The PREVAIL study randomized 1717 men (1715 treated) between September 2010 and September 2012. Australia, Japan, Singapore and South Korea enrolled 380/22.1% patients (Australia, 232/13.5%; Asia 148/8.6%). Statistically significant benefits of enzalutamide over placebo were shown for both co-primary endpoints [(OS interim analysis at 540 deaths: 29% reduction in risk of death; OS: HR 0.71; 95% CI: 0.59-0.83; P< 0.0001); (the concurrent rPFS final analysis: 81% reduction in risk of radiographic progression or death; rPFS: HR 0.19; 95% CI: 0.15-0.23; P< 0.0001)] in the overall intent-to-treat population of PREVAIL. Among Australian/Asian patients, enzalutamide demonstrated a benefit in both co-primary endpoints (OS: HR 0.62; 95% CI: 0.42-0.92; rPFS: HR 0.14; 95% CI: 0.08-0.25).
Conclusions: Enzalutamide significantly improved OS and rPFS in men with chemotherapy-naïve mCRPC progressing despite androgen deprivation therapy. Efficacy outcomes in the Australia/Asia subgroup were consistent with those in the overall population.