Go Kimura1, Junji Yonese2, Takashi Fukagai3, Tomomi Kamba4, Kazuo Nishimura5, Masahiro Nozawa6, Hank Mansbach7, Ad Theeuwes8, Tomasz M Beer9, Bertrand Tombal10, Takeshi Ueda11. 1. Department of Urology, Nippon Medical School, Tokyo, Japan. 2. Department of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. 3. Department of Urology, Showa University Koto Toyosu Hospital, Tokyo, Japan. 4. Department of Urology, Kyoto University Hospital, Kyoto, Japan. 5. Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. 6. Department of Urology, Kinki University Faculty of Medicine, Higashiosaka City, Osaka, Japan. 7. Clinical Development, Medivation, San Francisco, California, USA. 8. Biostatistics, Astellas Pharma Global Development, Leiden, The Netherlands. 9. OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA. 10. Division of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium. 11. Division of Urology, Chiba Cancer Center, Chiba, Japan.
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.
RCT Entities:
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.