Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial
Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial
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DOI：
10.1016/s0140-6736(16)32389-3
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发表时间：
2016-12-17
期刊：
影响因子：
168.9
通讯作者：
Ellis, Matthew J.
中科院分区：
文献类型：
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作者：
Robertson, John F. R.;Bondarenko, Igor M.;Ellis, Matthew J.
背景芳香酶抑制剂是激素受体阳性的局部晚期或转移性乳腺癌的标准治疗药物。我们研究了与阿那曲唑相比，选择性雌激素受体降解剂fulvestrant是否能改善绝经后未接受内分泌治疗的患者的无进展生存率。方法在这项第三阶段的随机双盲试验中，我们从20个国家的113家学术医院和社区中心招募了组织学证实的雌激素受体阳性或孕激素受体阳性或两者兼而有之的符合条件的晚期或转移性乳腺癌患者。符合条件的患者是内分泌治疗不成熟的患者，WHO表现状态为0-2，至少有一处可测量或不可测量的病变。使用计算机生成的随机方案，患者被随机分配到(1：1)组(500 mg肌肉注射；在第0、14、28天，然后每隔28天)或阿那曲唑(每天1 mg口服)。主要终点是无进展生存期，由实体瘤第1版的反应评估标准确定。1、在意向治疗人群中评估因疾病恶化或因任何原因死亡而进行手术或放射治疗的干预。对所有接受了至少一剂随机治疗(包括安慰剂)的患者的安全结果进行了评估。这项试验已在临床试验中注册。GOV，编号NCT01602380。结果在2012年10月17日至2014年7月11日期间，524名患者纳入了这项研究。在这些患者中，462名患者被随机分配(230名接受弗维斯特治疗，232名接受阿那曲唑治疗)。氟维斯特组的无进展生存期显著长于阿那曲唑组(风险比[HR]0。797，95%可信区间0。637-0。999，p=0。0486)。中位无进展存活率为16。6个月(95%可信区间13.83-20。99)在Fulvestrant组中为13。8个月(11.99-16。59)阿那曲唑组。最常见的不良事件是关节痛(富维斯特组38[17%]比阿那曲唑组24[10%])和潮热(富维斯特组26[11%]比阿那曲唑组24[10%])。Fulvestrant组的228名患者中有16名(7%)和阿那曲唑组的232名患者中的11名(5%)因不良事件而停止治疗。与第三代芳香化酶抑制剂相比，Interpretation Fulvestrant具有更好的疗效，是激素受体阳性的局部晚期或转移性乳腺癌患者的首选治疗方案，与第三代芳香酶抑制剂相比，后者是这些患者一线治疗的标准护理。
Background Aromatase inhibitors are a standard of care for hormone receptor-positive locally advanced or metastatic breast cancer. We investigated whether the selective oestrogen receptor degrader fulvestrant could improve progression-free survival compared with anastrozole in postmenopausal patients who had not received previous endocrine therapy.Methods In this phase 3, randomised, double-blind trial, we recruited eligible patients with histologically confi rmed oestrogen receptor-positive or progesterone receptor-positive, or both, locally advanced or metastatic breast cancer from 113 academic hospitals and community centres in 20 countries. Eligible patients were endocrine therapy-naive, with WHO performance status 0-2, and at least one measurable or non-measurable lesion. Patients were randomly assigned (1: 1) to fulvestrant (500 mg intramuscular injection; on days 0, 14, 28, then every 28 days thereafter) or anastrozole (1 mg orally daily) using a computer-generated randomisation scheme. The primary endpoint was progression-free survival, determined by Response Evaluation Criteria in Solid Tumors version 1 . 1, intervention by surgery or radiotherapy because of disease deterioration, or death from any cause, assessed in the intention-to-treat population. Safety outcomes were assessed in all patients who received at least one dose of randomised treatment (including placebo). This trial is registered with ClinicalTrials. gov, number NCT01602380.Findings Between Oct 17, 2012, and July 11, 2014, 524 patients were enrolled to this study. Of these, 462 patients were randomised (230 to receive fulvestrant and 232 to receive anastrozole). Progression-free survival was significantly longer in the fulvestrant group than in the anastrozole group (hazard ratio [HR] 0 . 797, 95% CI 0 . 637-0 . 999, p=0 . 0486). Median progression-free survival was 16 . 6 months (95% CI 13 . 83-20 . 99) in the fulvestrant group versus 13 . 8 months (11 . 99-16 . 59) in the anastrozole group. The most common adverse events were arthralgia (38 [17%] in the fulvestrant group vs 24 [10%] in the anastrozole group) and hot flushes (26 [11%] in the fulvestrant group vs 24 [10%] in the anastrozole group). 16 (7%) of 228 patients in in the fulvestrant group and 11 (5%) of 232 patients in the anastrozole group discontinued because of adverse events.Interpretation Fulvestrant has superior efficacy and is a preferred treatment option for patients with hormone receptor-positive locally advanced or metastatic breast cancer who have not received previous endocrine therapy compared with a third-generation aromatase inhibitor, a standard of care for first-line treatment of these patients.