Massachusetts General Hospital Cancer Center, Lawrence House, 55 Fruit St, LRH-302, Boston, MA 02114, USA.
J Clin Oncol. 2013 Apr 10;31(11):1398-404. doi: 10.1200/JCO.2012.44.7805. Epub 2013 Jan 28.
In 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.
We 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.
In 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.
This 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.
在激素依赖性绝经后乳腺癌患者中，标准辅助治疗包括 5 年的非甾体芳香酶抑制剂阿那曲唑和来曲唑。甾体抑制剂依西美坦与非甾体芳香酶抑制剂部分非交叉耐药，且具有轻度雄激素活性，在疗效和毒性方面可能优于阿那曲唑，特别是骨丢失较少。
我们设计了一项开放性、随机、III 期试验，比较 5 年依西美坦与阿那曲唑，采用双侧优效性检验来检测依西美坦在 5 年无事件生存（EFS）方面的 2.4%改善。次要终点包括总生存、远处无病生存、对侧新发原发性乳腺癌的发生率以及安全性。
该研究纳入了 7576 名女性（中位年龄 64.1 岁）。中位随访 4.1 年后，依西美坦组的 4 年 EFS 为 91%，阿那曲唑组为 91.2%（分层风险比，1.02；95%CI，0.87 至 1.18；P=0.85）。总体而言，远处无病生存和疾病特异性生存也相似。共有 31.6%的患者因不良反应、合并疾病或研究拒绝而停止治疗。骨质疏松/骨量减少、高甘油三酯血症、阴道出血和高胆固醇血症在依西美坦组较少见，而轻度肝功能异常和罕见的心房颤动发作在阿那曲唑组较少见。血管舒缩和肌肉骨骼症状在两组间相似。
这项甾体和非甾体芳香酶抑制剂类别的首次比较显示，在绝经后乳腺癌的 5 年初始辅助治疗中，两种药物在乳腺癌结局方面均无优势，这与 MA.27 的一个假说一致，但需要进一步证实。在骨骼方面的毒性较小与 MA.27 的一个假说一致，但需要进一步证实。依西美坦应被视为绝经后激素受体阳性乳腺癌的另一种辅助治疗选择。
