Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
Lancet Oncol. 2012 Oct;13(10):983-92. doi: 10.1016/S1470-2045(12)70379-0. Epub 2012 Sep 18.
Abiraterone acetate improved overall survival in metastatic castration-resistant prostate cancer at a preplanned interim analysis of the COU-AA-301 double-blind, placebo-controlled phase 3 study. Here, we present the final analysis of the study before crossover from placebo to abiraterone acetate (after 775 of the prespecified 797 death events).
Between May 8, 2008, and July 28, 2009, this study enrolled 1195 patients at 147 sites in 13 countries. Patients were eligible if they had metastatic castration-resistant prostate cancer progressing after docetaxel. Patients were stratified according to baseline Eastern Cooperative Oncology Group (ECOG) performance status, worst pain over the past 24 h on the Brief Pain Inventory-Short Form, number of previous chemotherapy regimens, and type of progression. Patients were randomly assigned (ratio 2:1) to receive either abiraterone acetate (1000 mg, once daily and orally) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone with a permuted block method via an interactive web response system. The primary endpoint was overall survival, analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00091442.
Of the 1195 eligible patients, 797 were randomly assigned to receive abiraterone acetate plus prednisone (abiraterone group) and 398 to receive placebo plus prednisone (placebo group). At median follow-up of 20·2 months (IQR 18·4-22·1), median overall survival for the abiraterone group was longer than in the placebo group (15·8 months [95% CI 14·8-17·0] vs 11·2 months [10·4-13·1]; hazard ratio [HR] 0·74, 95% CI 0·64-0·86; p<0·0001). Median time to PSA progression (8·5 months, 95% CI 8·3-11·1, in the abiraterone group vs 6·6 months, 5·6-8·3, in the placebo group; HR 0·63, 0·52-0·78; p<0·0001), median radiologic progression-free survival (5·6 months, 5·6-6·5, vs 3·6 months, 2·9-5·5; HR 0·66, 0·58-0·76; p<0·0001), and proportion of patients who had a PSA response (235 [29·5%] of 797 patients vs 22 [5·5%] of 398; p<0·0001) were all improved in the abiraterone group compared with the placebo group. The most common grade 3-4 adverse events were fatigue (72 [9%] of 791 patients in the abiraterone group vs 41 [10%] of 394 in the placebo group), anaemia (62 [8%] vs 32 [8%]), back pain (56 [7%] vs 40 [10%]), and bone pain (51 [6%] vs 31 [8%]).
This final analysis confirms that abiraterone acetate significantly prolongs overall survival in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel treatment. No new safety signals were identified with increased follow-up.
醋酸阿比特龙在 COU-AA-301 双盲、安慰剂对照的 3 期研究的预先计划的中期分析中改善了转移性去势抵抗性前列腺癌的总生存期。在这里，我们在从安慰剂交叉到醋酸阿比特龙（在规定的 797 例死亡事件中的 775 例之后）之前，对该研究进行了最终分析。
2008 年 5 月 8 日至 2009 年 7 月 28 日，这项研究在 13 个国家的 147 个地点招募了 1195 名患者。符合条件的患者是在接受多西他赛治疗后进展的转移性去势抵抗性前列腺癌。患者根据基线东部合作肿瘤组（ECOG）表现状态、过去 24 小时内简要疼痛量表（Brief Pain Inventory-Short Form）的最严重疼痛、之前化疗方案的数量和进展类型进行分层。患者以 2:1 的比例随机分配（比例）接受醋酸阿比特龙（1000mg，每天一次，口服）加泼尼松（5mg，每天两次，口服）或安慰剂加泼尼松，采用交互式网络响应系统进行置换块方法。主要终点是总生存期，在意向治疗人群中进行分析。这项研究在 ClinicalTrials.gov 上注册，编号为 NCT00091442。
在 1195 名合格患者中，797 名被随机分配接受醋酸阿比特龙加泼尼松（阿比特龙组），398 名接受安慰剂加泼尼松（安慰剂组）。中位随访时间为 20.2 个月（IQR 18.4-22.1），阿比特龙组的中位总生存期长于安慰剂组（15.8 个月[95%CI 14.8-17.0]比 11.2 个月[10.4-13.1]；风险比[HR]0.74，95%CI 0.64-0.86；p<0.0001）。PSA 进展时间中位数（8.5 个月，95%CI 8.3-11.1，在阿比特龙组与 6.6 个月，95%CI 5.6-8.3，在安慰剂组；HR 0.63，0.52-0.78；p<0.0001）、中位影像学无进展生存期（5.6 个月，5.6-6.5，与 3.6 个月，2.9-5.5；HR 0.66，0.58-0.76；p<0.0001）和 PSA 反应患者的比例（235[29.5%]797 例患者与 22[5.5%]398 例患者；p<0.0001）在阿比特龙组均优于安慰剂组。最常见的 3-4 级不良事件是疲劳（72[9%]791 例阿比特龙组患者与 41[10%]394 例安慰剂组患者）、贫血（62[8%]与 32[8%]）、背痛（56[7%]与 40[10%]）和骨痛（51[6%]与 31[8%]）。
这项最终分析证实，醋酸阿比特龙显著延长了转移性去势抵抗性前列腺癌患者的总生存期，这些患者在接受多西他赛后进展。随着随访时间的增加，没有发现新的安全信号。
