Double-blind, Randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: Results from EFECT
Double-blind, Randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: Results from EFECT
复制标题
DOI：
10.1200/jco.2007.13.5822
复制
发表时间：
2008-04-01
影响因子：
45.3
通讯作者：
Piccart, Martine
中科院分区：
文献类型：
--
作者：
Chia, Stephen;Gradishar, William;Piccart, Martine
目的第三代非甾体芳香化酶抑制剂（AIs）作为绝经后激素受体阳性（HR +）乳腺癌的辅助和一线治疗药物，已越来越多地被应用。由于许多患者随后经历进展或复发，重要的是要确定与AI failure.Materials和方法后的疗效剂芙仕得与依西美坦临床试验（EFECT）的评价是一个随机，双盲，安慰剂对照，多中心的III期临床试验氟维司群与依西美坦在绝经后妇女HR +晚期乳腺癌（ABC）进展或复发后非甾体类AI。主要终点是疾病进展时间（TTP）。使用氟维司群负荷剂量（LD）方案：第0天肌内注射500 mg，第14、28天250 mg，此后每28天250 mg。结果共693名妇女被随机分配到氟维司群（n = 351）或依西美坦（n = 342）。大约60%的患者既往接受过至少两种内分泌治疗。两组的中位TTP均为3.7个月（风险比= 0.963; 95% CI，0.819 - 1.133; P = 0.6531）。氟维司群和依西美坦的总体缓解率（7.4% v6.7%; P = 0.736）和临床获益率（32.2% v31.5%; P = 0.853）分别相似。临床获益的中位持续时间分别为9.3和8.3个月。两种治疗均耐受良好，不良事件发生率或生活质量无显著差异。药代动力学数据证实，达到稳态1个月内与LD的fulvestrant.Conclusion计划氟维司群LD和阿司美坦是同样积极和耐受性良好，在一个有意义的比例绝经后妇女与ABC谁经历了进展或复发治疗过程中与非甾体类AI。
Purpose The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR +) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure.Materials and Methods Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR + advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily.Results A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane ( n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups ( hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate ( 7.4% v 6.7%; P = .736) and clinical benefit rate ( 32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant.Conclusion Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.