Enzalutamide in Japanese patients with chemotherapy‐naïve, metastatic castration‐resistant prostate cancer: A post‐hoc analysis of the placebo‐controlled PREVAIL trial

Abstract

Objectives: To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. Methods: This was a post-hoc analysis of the phase 3, double-blind, placebocontrolled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-na€ ıve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary endpoints were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostatespecific antigen response (≥50% decline) and time to skeletal-related event.Results: Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95% confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7% of enzalutamide-treated men versus 21.2% of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90% confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6% of enzalutamide-and 6.1% of placebo-treated Japanese patients. Conclusion: Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL.

Patient preferences for treatment of castration-resistant prostate cancer in Japan: a discrete-choice experiment

“…Hence, patients who were healthy enough to participate and were interested in research may be over-represented in our sample, thereby raising the possibility of selection bias. While we could not confirm the extent to which the current study’s sample represented the broader Japanese population of CRPC patients, we made sure to recruit patients from institutions in both east and west Japan, and the clinical and demographic features of our sample (e.g., age, ECOG, BMI) were generally in line with those reported in prior studies [28, 29]. Although efforts were made to ensure a representative sample, we could not control the precise ratio of subgroups that may appear in the CRPC population.…”

Post hocanalysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer—updated results

“…Of the 1717 patients enrolled, 61 (enzalutamide arm, n = 28; placebo arm, n = 33) were from Japanese study sites. At the prespecified interim analysis for OS (at 540 deaths in the overall population; data cutoff, 16 September 2013), the treatment effects of enzalutamide were consistent with those in the overall population (1): enzalutamide reduced the risk of death by 29% [hazard ratio (HR), 0.71; 95% confidence interval (CI), 0.60–0.84] and risk of investigator-assessed radiographic progression or death by 57% (HR, 0.43; 95% CI, 0.18–1.04) in Japanese patients (2). Longer term efficacy and safety up to the prespecified number of deaths in the final analysis were recently reported for the overall PREVAIL population, demonstrating continued benefit of enzalutamide over placebo (3).…”

“…Baseline patient demographics have been published (2) and are presented in Table 1. In this follow-up analysis of Japanese patients, with an additional 9 months of data, including 5 months of data after 17 of 33 placebo-treated patients in the open-label extension crossed over to enzalutamide, enzalutamide reduced the risk of death by 35% (HR, 0.65; 95% CI, 0.28–1.51; Fig.…”

“…of prior unique anti-androgen therapies (%) ≤157.142.4 ≥242.957.6No. of prior unique hormone therapies (%) ≤242.933.3 ≥357.166.7Prior radical prostatectomy (%)3.63.0Bone disease (%)96.4100 ≥10 bone metastases50.036.4Soft-tissue disease—lymph node, visceral or other (%)46.436.4BPI-SF Q3, Brief Pain Inventory Short Form question 3; ECOG PS, Eastern Cooperative Oncology Group Performance Status; PSA, prostate-specific antigen. a Reproduced from Kimura et al (2), under the Attribution-NonCommercial-NoDerivatives 4.0 International license. Copyright 2016, The Authors and John Wiley & Sons Australia, Ltd, on behalf of the Japanese Urological Association.…”

“…We recently reported treatment effects and safety from a post hoc analysis of Japanese patients enrolled in PREVAIL at the interim analysis (2). Of the 1717 patients enrolled, 61 (enzalutamide arm, n = 28; placebo arm, n = 33) were from Japanese study sites.…”