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, 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.

• Authors: Go Kimura, Junji Yonese, Takashi Fukagai, Tomomi Kamba, Kazuo Nishimura, Masahiro Nozawa, Hank Mansbach, Ad Theeuwes, Tomasz M Beer, Bertrand Tombal, Takeshi Ueda
• Journal: International journal of urology : official journal of the Japanese Urological Association (Int J Urol) Vol. 23 Issue 5 Pg. 395-403 (05 2016) ISSN: 1442-2042 [Electronic] Australia
• PMID: 27018069 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
• Copyright: © 2016 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.

Chemical References

• Antineoplastic Agents
• Benzamides
• Nitriles
• Phenylthiohydantoin
• enzalutamide

Topics

• Antineoplastic Agents (adverse effects, therapeutic use)
• Benzamides
• Disease-Free Survival
• Double-Blind Method
• Humans
• Japan
• Male
• Nitriles
• Phenylthiohydantoin (adverse effects, analogs & derivatives, therapeutic use)
• Prostatic Neoplasms, Castration-Resistant (drug therapy)
• Treatment Outcome