阿比特龙与转移性前列腺癌患者的生存获益
Abiraterone and increased survival in metastatic prostate cancer.
机构信息
Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, United Kingdom.
出版信息
N Engl J Med. 2011 May 26;364(21):1995-2005. doi: 10.1056/NEJMoa1014618.
BACKGROUND
Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy.
METHODS
We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate.
RESULTS
After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate-prednisone group than in the placebo-prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate-prednisone group than in the placebo-prednisone group.
CONCLUSIONS
The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 ClinicalTrials.gov number, NCT00638690.).
背景
外源性雄激素的生物合成可能有助于去势抵抗性前列腺癌的进展。我们评估了雄激素生物合成抑制剂醋酸阿比特龙是否能延长已接受化疗的转移性去势抵抗性前列腺癌患者的总生存期。
方法
我们以 2:1 的比例随机分配 1195 名先前接受过多西他赛治疗的患者，每日两次接受 5mg 泼尼松与 1000mg 醋酸阿比特龙（797 名患者）或安慰剂（398 名患者）联合治疗。主要终点为总生存期。次要终点包括前列腺特异性抗原（PSA）进展时间（根据预定标准 PSA 水平升高）、根据影像学结果确定的无进展生存期（根据预定标准）以及 PSA 反应率。
结果
中位随访 12.8 个月后，醋酸阿比特龙-泼尼松组的总生存期长于安慰剂-泼尼松组（14.8 个月比 10.9 个月；风险比，0.65；95%置信区间，0.54 至 0.77；P<0.001）。中期分析时数据被揭盲，因为这些结果超过了研究终止的预先计划标准。所有次要终点，包括 PSA 进展时间（10.2 个月比 6.6 个月；P<0.001）、无进展生存期（5.6 个月比 3.6 个月；P<0.001）和 PSA 反应率（29%比 6%；P<0.001），均有利于治疗组。醋酸阿比特龙-泼尼松组更频繁地报告了盐皮质激素相关的不良事件，包括液体潴留、高血压和低钾血症。
结论
醋酸阿比特龙抑制雄激素生物合成可延长先前接受化疗的转移性去势抵抗性前列腺癌患者的总生存期。（由 Cougar Biotechnology 资助；COU-AA-301 ClinicalTrials.gov 编号，NCT00638690。）
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