醋酸阿比特龙联合泼尼松对比安慰剂联合泼尼松治疗化疗初治转移性去势抵抗性前列腺癌患者（COU-AA-302）：一项随机、双盲、安慰剂对照的 3 期研究的最终总生存分析。
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.
机构信息
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
出版信息
Lancet Oncol. 2015 Feb;16(2):152-60. doi: 10.1016/S1470-2045(14)71205-7. Epub 2015 Jan 16.
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 prespecified 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 [<1%]), and hypertension (25 [5%] vs 17 [3%]).
INTERPRETATION
In this randomised phase 3 trial with a median follow-up of more than 4 years, treatment with abiraterone acetate prolonged overall survival compared with prednisone alone by a margin that was both clinically and statistically significant. These results further support the favourable safety profile of abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer.
FUNDING
Janssen Research & Development.
背景
在 COU-AA-302 试验的中期分析中，醋酸阿比特龙联合泼尼松与安慰剂联合泼尼松相比，显著改善了化疗初治去势抵抗性前列腺癌患者的影像学无进展生存期。在此，我们报告了该试验的预先设定的最终分析，评估了醋酸阿比特龙联合泼尼松对总生存期、阿片类药物使用时间和其他后续治疗的使用的影响。
方法
在这项安慰剂对照、双盲、随机 3 期研究中，1088 例化疗初治前列腺癌患者（按东部肿瘤协作组体能状态（0 与 1）分层）以随机区组的方式按 1:1 的比例随机分配，接受醋酸阿比特龙（1000mg 每日一次）联合泼尼松（5mg 每日两次；醋酸阿比特龙组）或安慰剂联合泼尼松（安慰剂组）治疗。主要终点是影像学无进展生存期和总生存期，在意向治疗人群中进行分析。该研究在 ClinicalTrials.gov 注册，编号为 NCT00887198。
结果
中位随访 49.2 个月（IQR 47.0-51.8）时，773 例死亡事件中有 741 例（96%）预先设定为最终分析：醋酸阿比特龙组 546 例中有 354 例（65%），安慰剂组 542 例中有 387 例（71%）。最初单独接受泼尼松治疗的 238 例（44%）患者随后根据方案（93 例）或后续治疗（145 例）接受了醋酸阿比特龙联合泼尼松的交叉治疗。总体而言，醋酸阿比特龙组 365 例（67%）和安慰剂组 435 例（80%）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长于安慰剂组（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）。特别关注的最常见的 3-4 级不良事件是心脏疾病（醋酸阿比特龙组 542 例中有 41 例[8%]，安慰剂组 540 例中有 20 例[4%]）、丙氨酸氨基转移酶升高（32 例[6%]vs 4 例[<1%]）和高血压（25 例[5%]vs 17 例[3%]）。
解释
在这项中位随访超过 4 年的随机 3 期试验中，与单独使用泼尼松相比，醋酸阿比特龙治疗延长了总生存期，且在临床和统计学上均有显著意义。这些结果进一步支持醋酸阿比特龙在化疗初治转移性去势抵抗性前列腺癌患者中的良好安全性。
资金来源
杨森研发。
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