Subgroup analyses of Japanese patients from the PREVAIL trial of enzalutamide (ENZA) in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC).

Abstract

265 Background: In PREVAIL, an international phase 3 randomized trial, treatment with ENZA decreased the risk of radiographic progression or death by 81% and the risk of death by 29% compared with placebo. We evaluated efficacy, safety and pharmacokinetic exposure with ENZA in the Japanese subgroup of patients participating in PREVAIL. Methods: Asymptomatic or mildly symptomatic chemotherapy-naïve patients with mCRPC progressing on androgen deprivation therapies were randomized 1:1 to ENZA 160 mg or placebo until discontinuation upon radiographic progression or initiation of chemotherapy. Continued androgen-deprivation therapy was required. Coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS). Prostate-specific antigen (PSA) response was defined as a confirmed ≥50% reduction from baseline to nadir. Results: A total of 1,717 patients (ENZA: 872, placebo: 845) were randomized in PREVAIL, of which 61 patients were Japanese (ENZA: 28, placebo: 33). The trial was halted after a planned interim analysis at which hazard ratios calculated for OS (0.71; 95%CI: 0.60-0.84) and rPFS (0.19; 95%CI: 0.15-0.23) showed significant benefit of ENZA vs placebo. Hazard ratios for OS and rPFS in Japanese patients were 0.60 (95%CI: 0.20-1.78) and 0.29 (95%CI: 0.030-2.95), respectively. Time to chemotherapy was delayed from a median 10 months on placebo vs not yet reached on ENZA, with a hazard ratio of 0.46 (95%CI: 0.22-0.96). PSA responses were more common in Japanese patients receiving ENZA (61%) vs placebo (21%) (treatment effect = 39.5%; 95%CI: 16.7%-62.3%). Plasma concentration of ENZA was slightly higher in the Japanese subgroup: geometric mean Cmin= 13.8 µg/mL vs 12.3 µg/mL in the non-Japanese cohort at 13 weeks. In the Japanese subgroup adverse events (AEs) ≥ Grade 3 were reported by 9/28 patients (32%) on ENZA vs 13/33 patients (39%) on placebo. Treatment-related AEs ≥ Grade 3 were rare: in the ENZA arm (1/28; 3.6%) and in the placebo arm (2/33; 6.1%). Conclusions: Theefficacy and safety results in the Japanese subgroup were generally consistent with the overall results from the PREVAIL trial. Clinical trial information: NCT01212991.