Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27-A Randomized Controlled Phase III Trial
Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27-A Randomized Controlled Phase III Trial
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DOI：
10.1200/jco.2012.44.7805
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发表时间：
2013-04-10
影响因子：
45.3
通讯作者：
Shepherd, Lois E.
中科院分区：
文献类型：
--
作者：
Goss, Paul E.;Ingle, James N.;Shepherd, Lois E.
对绝经后乳腺癌患者，标准的辅助治疗包括5年的非甾体芳香化酶抑制剂阿那曲唑和来曲唑。甾体类抑制剂阿司美坦与非甾体芳香酶抑制剂部分非交叉耐药，是一种温和的雄激素，在疗效和毒性方面可能上级阿那曲唑，特别是骨丢失较少。一项为期5年的阿司美坦与阿那曲唑的III期试验，采用双侧优效性检验，检测阿司美坦在5-年无事件生存率（EFS）。次要目标包括评估总生存率，无远处转移生存率，对侧新的原发性乳腺癌的发病率，和safety.ResultsIn研究，7,576名妇女（中位年龄，64.1岁）参加。中位随访时间为4.1年，阿司美坦的4年EFS为91%，阿那曲唑为91.2%（分层风险比，1.02; 95%CI，0.87 - 1.18; P = 0.85）。总体而言，无远处转移生存期和疾病特异性生存期也相似。总体而言，31.6%的患者因不良反应、伴随疾病或研究拒绝而停止治疗。骨质疏松/骨量减少、高胆固醇血症、阴道出血和高胆固醇血症在阿司美坦组中的发生率较低，而轻度肝功能异常和罕见房颤发作在阿那曲唑组中的发生率较低。血管和肌肉骨骼症状arms.ConclusionThis第一次比较甾体类和非甾体类芳香化酶抑制剂显示既不是上级乳腺癌的结果作为5年的初始辅助治疗绝经后乳腺癌的双向测试。对骨的毒性较小与MA背后的一个假设相符。27、需要确认依西美坦应被视为绝经后激素受体阳性乳腺癌的另一种前期辅助治疗选择。J Clin Oncol 31：1398-1404. (C)2013年美国临床肿瘤学会
PurposeIn patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss.Patients and MethodsWe designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety.ResultsIn the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms.ConclusionThis first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA. 27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer. J Clin Oncol 31:1398-1404. (C) 2013 by American Society of Clinical Oncology