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Enzalutamide in Japanese patients with chemotherapy‐naïve, metastatic castration‐resistant prostate cancer: A post‐hoc analysis of the placebo‐controlled PREVAIL trial
Author(s) -
Kimura Go,
Yonese Junji,
Fukagai Takashi,
Kamba Tomomi,
Nishimura Kazuo,
Nozawa Masahiro,
Mansbach Hank,
Theeuwes Ad,
Beer Tomasz M,
Tombal Bertrand,
Ueda Takeshi
Publication year - 2016
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/iju.13072
Subject(s) - enzalutamide , medicine , prostate cancer , placebo , hazard ratio , oncology , post hoc analysis , prostate specific antigen , androgen deprivation therapy , chemotherapy , urology , confidence interval , surgery , cancer , pathology , androgen receptor , alternative medicine
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, placebo‐controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy‐naïve 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 end‐points were investigator‐assessed radiographic progression‐free survival, time to initiation of chemotherapy, time to prostate‐specific antigen progression, prostate‐specific 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.