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

Go Kimura, Junji Yonese, Takashi Fukagai, Tomomi Kamba, Kazuo Nishimura, Masahiro Nozawa, Hank Mansbach, Ad Theeuwes, Tomasz M. Beer, Bertrand Tombal, Takeshi Ueda

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    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, 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.

    Original languageEnglish (US)
    Pages (from-to)395-403
    Number of pages9
    JournalInternational Journal of Urology
    Volume23
    Issue number5
    DOIs
    StatePublished - May 1 2016

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    Keywords

    • Antineoplastic agents
    • Disease-free survival
    • Japan
    • MDV 3100
    • Prostatic neoplasms, castration-resistant

    ASJC Scopus subject areas

    • Urology

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