Abiraterone in metastatic prostate cancer without previous chemotherapy.
Abiraterone in metastatic prostate cancer without previous chemotherapy.
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DOI：
10.1056/nejmoa1209096
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发表时间：
2013-01-10
期刊：
影响因子：
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通讯作者：
COU-AA-302 Investigators
中科院分区：
文献类型：
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作者：
Ryan CJ;Smith MR;de Bono JS;Molina A;Logothetis CJ;de Souza P;Fizazi K;Mainwaring P;Piulats JM;Ng S;Carles J;Mulders PF;Basch E;Small EJ;Saad F;Schrijvers D;Van Poppel H;Mukherjee SD;Suttmann H;Gerritsen WR;Flaig TW;George DJ;Yu EY;Efstathiou E;Pantuck A;Winquist E;Higano CS;Taplin ME;Park Y;Kheoh T;Griffin T;Scher HI;Rathkopf DE;COU-AA-302 Investigators
阿比特龙是一种雄激素生物合成抑制剂，可改善化疗后转移性去势抵抗前列腺癌(MCRPC)的总生存率(OS)。许多mCRPC患者从未接受过化疗，因此不能受益于醋酸阿比特龙；我们在没有接受过化疗的mCRPC患者中评估了这种药物。在这项双盲研究中，1088名患者被随机分成1：1组，分别服用醋酸阿比特龙(1000毫克)和泼尼松(每日两次，每次5毫克)或安慰剂+泼尼松。共同的主要终点是放射学无进展生存期(RPFS)和OS。次要终点测量了mCRPC进展的临床相关标志物。患者报告的结果包括疼痛进展和生活质量。在对43%的OS事件进行计划的中期分析(IA)后，这项研究没有受到影响。使用阿比特龙-泼尼松治疗后，放射学进展或死亡的风险降低了57%(风险比[HR]，0.43；95%可信区间[CI]：0.35至0.52；P<；0.001；13%OS Events IA)，死亡风险估计降低了25%(HR，0.75；95%CI：0.61至0.93；P=0.009；43%OS Events IA)。次级终点支持醋酸阿比特龙-泼尼松的优势：细胞毒性化疗开始的时间、阿片类药物用于癌症相关疼痛、前列腺特异性抗原进展(全部P<；0.001)和性能状况恶化(P=0.005)。自我报告的疼痛进展时间和患者功能状态恶化倾向于醋酸阿比特龙-泼尼松(P=0.003和P=0.05)。与3/4级盐皮质激素相关的不良事件和肝功能检测异常在服用醋酸阿比特龙-泼尼松的患者中更为常见。在mCRPC中，醋酸阿比特龙产生OS和rPFS益处，并显著延迟临床恶化和开始化疗。
Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) post-chemotherapy. Many mCRPC patients never receive chemotherapy and thus cannot benefit from abiraterone acetate; we evaluated this agent in mCRPC patients who had not received chemotherapy. In this double-blind study, 1088 patients were randomized 1:1 to abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. Co-primary end points were radiographic progression-free survival (rPFS) and OS. Secondary end points measured clinically relevant landmarks of mCRPC progression. Patient-reported outcomes included pain progression and quality of life. The study was unblinded after a planned interim analysis (IA) at 43% of OS events. Treatment with abiraterone acetate-prednisone resulted in a 57% reduction in the risk of radiographic progression or death (hazard ratio [HR], 0.43; 95% confidence interval [CI]: 0.35 to 0.52; P<0.001; 13% OS events IA) and an estimated 25% decrease in the risk of death (HR, 0.75; 95% CI: 0.61 to 0.93; P=0.009; 43% OS events IA). Secondary end points supported superiority of abiraterone acetate-prednisone: time to cytotoxic chemotherapy initiation, opiate use for cancer-related pain, prostate-specific antigen progression (all P<0.001) and performance status deterioration (P=0.005). Self-reported time to pain progression and patient functional status degradation favored abiraterone acetate-prednisone (P=0.05 and P=0.003). Grade 3/4 mineralocorticoid-related adverse events and liver function test abnormalities were more common with abiraterone acetate-prednisone. Abiraterone acetate produces OS and rPFS benefits, as well as significant delays in clinical deterioration and initiation of chemotherapy, in mCRPC.