Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study
Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study
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DOI：
10.1016/s1470-2045(14)71205-7
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发表时间：
2015-02-01
期刊：
影响因子：
51.1
通讯作者：
Rathkopf, Dana E.
中科院分区：
文献类型：
--
作者：
Ryan, Charles J.;Smith, Matthew R.;Rathkopf, Dana E.
在coua - aa -302试验的中期分析中，与安慰剂加强的松相比，醋酸阿比特龙加强的松显著提高了化疗初期阉割抵抗性前列腺癌患者的放射学无进展生存期。在这里，我们提出了预先指定的试验最终分析，评估醋酸阿比特龙加强的松对总生存期、阿片类药物使用时间和其他后续治疗的影响。方法：在这项安慰剂对照、双盲、随机的3期研究中，1088名无症状或轻度症状的前列腺癌化疗初期患者根据Eastern Cooperative Oncology的表现状况（0比1）进行分层，通过网络反应系统按1:1的比例随机分配到一个排列块分配方案中，接受醋酸阿比特龙（1000mg每日一次）+强的松(5mg每日两次；醋酸阿比特龙组)或安慰剂加强的松组（安慰剂组）。主要终点是放射学无进展生存期和意向治疗人群的总生存期。该研究已在ClinicalTrials.gov注册，注册号为NCT00887198。中位随访时间为49。2个月（IQR为47.0-51.8），在最终分析的预先指定的773例死亡事件中观察到741例（96%）：546例醋酸阿比特龙组中有354例（65%），542例安慰剂组中有387例（71%）。238例（44%）患者最初单独接受强的松，随后接受醋酸阿比特龙加强的松作为交叉治疗（93例）或作为后续治疗（145例）。总体而言，365例（67%）醋酸阿比特龙组患者和435例（80%）安慰剂组患者接受了一种或多种批准药物的后续治疗。醋酸阿比特龙组的中位总生存期明显高于安慰剂组（34.7个月[95% CI 32.7-36.8] vs 30.3个月[28.7-33.3]；风险比0.81 [95% CI 0.70-0.93]; p = 0.0033）。最常见的3-4级不良事件是心脏疾病（542例患者中有41例[8%]醋酸阿比特龙组对540例患者中有20例[4%]安慰剂组），丙氨酸转氨酶升高（32例[6%]对4例[4%]）。
Background Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall survival, time to opiate use, and use of other subsequent therapies.Methods In this placebo-controlled, double-blind, randomised phase 3 study, 1088 asymptomatic or mildly symptomatic patients with chemotherapy-naive prostate cancer stratified by Eastern Cooperative Oncology performance status (0 vs 1) were randomly assigned with a permuted block allocation scheme via a web response system in a 1:1 ratio to receive either abiraterone acetate (1000 mg once daily) plus prednisone (5 mg twice daily; abiraterone acetate group) or placebo plus prednisone (placebo group). Coprimary endpoints were radiographic progression-free survival and overall survival analysed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00887198.Findings At a median follow-up of 49 . 2 months (IQR 47.0-51.8), 741 (96%) of the prespecifi ed 773 death events for the final analysis had been observed: 354 (65%) of 546 patients in the abiraterone acetate group and 387 (71%) of 542 in the placebo group. 238 (44%) patients initially receiving prednisone alone subsequently received abiraterone acetate plus prednisone as crossover per protocol (93 patients) or as subsequent therapy (145 patients). Overall, 365 (67%) patients in the abiraterone acetate group and 435 (80%) in the placebo group received subsequent treatment with one or more approved agents. Median overall survival was significantly longer in the abiraterone acetate group than in the placebo group (34.7 months [95% CI 32.7-36.8] vs 30.3 months [28.7-33.3]; hazard ratio 0.81 [95% CI 0.70-0.93]; p = 0.0033). The most common grade 3-4 adverse events of special interest were cardiac disorders (41 [8%] of 542 patients in the abiraterone acetate group vs 20 [4%] of 540 patients in the placebo group), increased alanine aminotransferase (32 [6%] vs four [