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

被引：20

作者：

Kimura, Go ^{[1
]}

Yonese, Junji ^{[2
]}

Fukagai, Takashi ^{[3
]}

Kamba, Tomomi ^{[4
]}

Nishimura, Kazuo ^{[5
]}

Nozawa, Masahiro ^{[6
]}

Mansbach, Hank ^{[7
]}

Theeuwes, Ad ^{[8
]}

Beer, Tomasz M. ^{[9
]}

Tombal, Bertrand ^{[10
]}

Ueda, Takeshi ^{[11
]}

机构：

[1] Nippon Med Sch, Dept Urol, Tokyo 1138603, Japan

[2] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Urol, Tokyo, Japan

[3] Showa Univ, Koto Toyosu Hosp, Dept Urol, Tokyo, Japan

[4] Kyoto Univ Hosp, Dept Urol, Kyoto 606, Japan

[5] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Urol, Osaka, Japan

[6] Kinki Univ, Fac Med, Dept Urol, Higashiosaka, Osaka 577, Japan

[7] Medivation, Clin Dev, San Francisco, CA USA

[8] Astellas Pharma Global Dev, Biostat, Leiden, Netherlands

[9] Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, Portland, OR 97201 USA

[10] Clin Univ St Luc, Div Urol, B-1200 Brussels, Belgium

[11] Chiba Canc Ctr, Div Urol, 666-2 Nitonacho, Chiba 2608717, Japan

来源：

INTERNATIONAL JOURNAL OF UROLOGY | 2016年 / 23卷 / 05期

关键词：

antineoplastic agents; disease-free survival; Japan; MDV; 3100; prostatic neoplasms; castration-resistant; COMMUNITY-BASED POPULATION; MEN; ANTIGEN; ANTIANDROGEN; PREDNISONE; SURVIVAL;

D O I：

10.1111/iju.13072

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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-naive 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.

引用

页码：395 / 403

页数：9

共 29 条

[1]

Beer TM, 2014, NEW ENGL J MED, V371, P424, DOI 10.1056/NEJMoa1405095

[2] Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: Updated survival in the TAX 327 study [J].