Abiraterone Acetate in Combination with Prednisone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer: US Food and Drug Administration Drug Approval Summary
Abiraterone Acetate in Combination with Prednisone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer: US Food and Drug Administration Drug Approval Summary
复制标题
DOI：
10.1158/1078-0432.ccr-13-2134
复制
发表时间：
2013-12-15
影响因子：
11.5
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
--
作者：
Kluetz, Paul G.;Ning, Yang-Min;Pazdur, Richard
2012年12月10日，美国食品和药物管理局完全批准了醋酸阿比特龙(Zytiga片剂；Janssen Biotech，Inc.)的修改适应症。联合泼尼松治疗耐去势转移性前列腺癌(MCRPC)。批准是基于临床试验cou-AA-302，该试验随机将无症状或轻度症状的患者分配给接受化疗的初治mCRPC且没有内脏转移的阿比特龙+强的松(N=546)或安慰剂+强的松(N=542)。治疗终点为放射学无进展生存期(RPFS)和总生存期(OS)。安慰剂组的中位RPFS为8.3月，而安慰剂组尚未达到(HR，0.43[95%可信区间(CI)0.35-0.52]；P<；0.0001)。一项预先指定的中期分析显示，有利于阿比特龙的患者的OS有所改善[HR，0.79(95%CI，0.66-0.96)]，但在统计学意义上没有超过O‘Brien-Fleming边界。安全性数据证实了已知的醋酸阿比特龙不良反应情况。完全批准是基于对rPFS的巨大影响，OS的有利趋势，以及多个次级终端和探索性患者报告的疼痛数据的内部一致性。这是mCRPC第一次批准使用rPFS作为主要终点的药物。重要的是，这一批准是在先前具有统计意义的OS福利的背景下批准的，该福利构成了2011年4月28日最初的基础，即批准将醋酸阿比特龙用于先前接受过含有多西他赛的化疗的mCRPC患者。(C)2013年AACR。
On December 10, 2012, the U. S. Food and Drug Administration granted full approval for a modified indication for abiraterone acetate (Zytiga tablets; Janssen Biotech, Inc.) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The approval was based on clinical trial COU-AA-302, which randomly allocated asymptomatic or mildly symptomatic patients with chemotherapy-naive mCRPC and no visceral metastases to either abiraterone acetate plus prednisone (N = 546) or placebo plus prednisone (N 542). The coprimary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS). The median rPFS was 8.3 months in the placebo arm and had not yet been reached in the abiraterone acetate arm {HR, 0.43 [95% confidence interval (CI) 0.35-0.52]; P < 0.0001}. A prespecified interim analysis demonstrated an improvement in OS favoring the abiraterone acetate arm [HR, 0.79 (95% CI, 0.66-0.96)] but did not cross the O'Brien-Fleming boundary for statistical significance. Safety data confirmed the known adverse reaction profile of abiraterone acetate. Full approval was granted on the basis of a large magnitude of effect on rPFS, a favorable trend in OS, and internal consistency across multiple secondary endpoints and exploratory patient-reported pain data. This is the first drug approval for mCRPC to use rPFS as the primary endpoint. Importantly, this approval was granted in the context of a prior statistically significant OS benefit that formed the basis of the original April 28, 2011, approval of abiraterone acetate for patients with mCRPC who had received prior chemotherapy containing docetaxel. (C) 2013 AACR.