title: Enzalutamide in Japanese patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer: A post-hoc analysis of the placebo-controlled PREVAIL trial.
abstract: To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL.
authors.affiliation: Department of Urology, Nippon Medical School, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Kimura
authors.affiliation: Department of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yonese
authors.affiliation: Department of Urology, Showa University Koto Toyosu Hospital, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukagai
authors.affiliation: Department of Urology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kamba
authors.affiliation: Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Urology, Kinki University Faculty of Medicine, Higashiosaka City, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nozawa
authors.affiliation: Clinical Development, Medivation, San Francisco, California, USA.
authors.forename: Hank
authors.initials: H
authors.lastname: Mansbach
authors.affiliation: Biostatistics, Astellas Pharma Global Development, Leiden, The Netherlands.
authors.forename: Ad
authors.initials: A
authors.lastname: Theeuwes
authors.affiliation: OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
authors.affiliation: Division of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
authors.affiliation: Division of Urology, Chiba Cancer Center, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueda
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D007564:Japan; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: Japan; MDV 3100; antineoplastic agents; disease-free survival; prostatic neoplasms, castration-resistant