TY - JOUR
T1 - Enzalutamide in Japanese patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer
T2 - A post-hoc analysis of the placebo-controlled PREVAIL trial
AU - Kimura, Go
AU - Yonese, Junji
AU - Fukagai, Takashi
AU - Kamba, Tomomi
AU - Nishimura, Kazuo
AU - Nozawa, Masahiro
AU - Mansbach, Hank
AU - Theeuwes, Ad
AU - Beer, Tomasz M.
AU - Tombal, Bertrand
AU - Ueda, Takeshi
N1 - Funding Information:
PREVAIL was funded by Medivation and Astellas Pharma, the co-developers of enzalutamide. Medical writing and editorial support funded by both sponsor companies was provided by Stephanie Vadasz, Ph.D., and Shannon Davis of Infusion Communications.
Publisher Copyright:
© 2016 The Authors.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Antineoplastic agents
KW - Disease-free survival
KW - Japan
KW - MDV 3100
KW - Prostatic neoplasms, castration-resistant
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U2 - 10.1111/iju.13072
DO - 10.1111/iju.13072
M3 - Article
C2 - 27018069
AN - SCOPUS:84962203743
SN - 0919-8172
VL - 23
SP - 395
EP - 403
JO - International Journal of Urology
JF - International Journal of Urology
IS - 5
ER -