286P Efficacy, safety and pharmacokinetics (PK) of enzalutamide (ENZ) vs placebo (PL) in chemotherapy-naïve patients (pts) with progressive metastatic castration-resistant prostate cancer (mCRPC): An Asian multinational study

Abstract

Background: In PREVAIL, pts with progressive mCRPC had significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) on ENZ vs PL (Beer TM et al, N Engl J Med, 2014). The efficacy, safety and PK of ENZ vs PL were evaluated in a similar patient population in China, Taiwan and South Korea. Method(s): Pts with asymptomatic/mildly symptomatic progressive mCRPC were randomised 1:1 to ENZ (160 mg/day) or PL. Interim results are presented. The primary end point was time to prostate-specific antigen (PSA) progression. Secondary end points were OS (randomisation to death) and rPFS (randomisation to radiographic progression or death). Safety and PK (pts in China only) were also assessed. Result(s): 409 pts were randomised; 209 ENZ/200 PL, with similar baseline characteristics. Median time to PSA progression was 7.5 months for ENZ vs 2.9 for PL (hazard ratio [HR] 0.36; 95% confidence interval [CI] 0.27, 0.50; p<0.0001). Median OS was not yet reached (NYR) for ENZ and PL (HR 0.35; 95% CI 0.17, 0.70; p=0.0021). Median rPFS was NYR for ENZ and 4.7 months for PL (HR 0.28; 95% CI 0.19, 0.42; p<0.0001). Median time on treatment was 6.6 months for ENZ; 3.7 for PL. Slightly more ENZ than PL pts reported >=1 treatment-emergent adverse event (TEAE) [84.7% vs 80.5%]. More PL than ENZ pts reported >=1 serious TEAE (24.5% vs 17.2%); grade >=3 TEAE (29.5% vs 24.4%) and TEAE leading to treatment discontinuation (17.0% vs 12.9%). Seventeen pts were evaluable for PK analysis of ENZ, metabolite 2 (M2), and ENZ +M2 after single and multiple doses of ENZ (Table). Conclusion(s): ENZ showed significant efficacy over PL and was generally well tolerated. As the difference in PK in this study vs other studies is small and not clinically relevant, ENZ 160 mg dosing is appropriate in the Asian population. The trial was stopped early as it reached its primary objective.