Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women - A prospective combined analysis of two multicenter trials
Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women - A prospective combined analysis of two multicenter trials
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DOI：
10.1002/cncr.11468
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发表时间：
2003-07-15
期刊：
影响因子：
6.2
通讯作者：
Morris, C
中科院分区：
文献类型：
--
作者：
Robertson, JFR;Osborne, CK;Morris, C
背景氟维司群（ICI 182，780）是一种新型雌激素受体（ER）拮抗剂，可下调ER，无已知的激动剂作用。作者报告了前瞻性计划的对2项III期试验数据的联合分析，比较了氟维司群每月250 mg（n = 428）和阿那曲唑每日1 mg（n = 423）在患有晚期乳腺癌（ABC）的绝经后女性中的应用，这些女性之前在接受内分泌治疗后病情进展。方法。主要终点为至疾病进展时间（TTP）。次要终点包括客观缓解（OR）、缓解持续时间（DOR）和耐受性。试验旨在证明氟维司群优于阿那曲唑。采用回顾性统计检验确定氟维司群与阿那曲唑相比的非劣效性。在中位随访15.1个月时，每个治疗组中约83%的患者发生进展。氟维司群组的中位TTP为5.5个月，阿那曲唑组为4.1个月，氟维司群和阿那曲唑的OR率分别为19.2%和16.5%（尽管治疗之间的差异无统计学意义）。对应答患者进行进一步随访（中位数，22.1个月），以获得关于DOR的更完整信息;氟维司群组和阿那曲唑组中，治疗应答患者的中位DOR（从随机化至疾病进展）分别为16.7个月和13.7个月。在DOR的统计分析中（使用所有随机化患者;从缓解开始至疾病进展），氟维司群组患者的DOR显著长于阿那曲唑组患者。两种药物均耐受良好;氟维司群组和阿那曲唑组因药物相关不良事件而退出研究的比例分别为0.9%和1.2%。氟维司群组关节疾病的发生率显著较低（P = 0.0036），结论。氟维司群耐受性良好，在ABC患者的二线治疗中至少与阿那曲唑一样有效。这种新的绝经后治疗方法可能为绝经后ABC提供一种有价值的治疗选择（C）2003美国癌症协会。
BACKGROUND. Fulvestrant (ICI 182,780) is a new type of estrogen receptor (ER) antagonist that down-regulates the ER and has no known agonist effects. The authors report the prospectively planned combined analysis of data from 2 Phase III trials comparing fulvestrant 250 mg monthly (n = 428) and anastrozole 1 mg daily (n = 423) in postmenopausal women with advanced breast carcinoma (ABC) who previously had progressed after receiving endocrine treatment.METHODS. The primary endpoint was time to progression (TTP). Secondary end-points included objective response (OR), duration of response (DOR), and tolerability. The trials were designed to demonstrate superiority of fulvestrant over anastrozole. Noninferiority of fulvestrant versus anastrozole was determined using a retrospectively applied statistical test.RESULTS. At a median follow-up of 15.1 months, approximate to 83% of patients in each treatment arm had progressed. The median TTP was 5.5 months in the fulvestrant group and 4.1 months in the anastrozole group, and the OR rates were 19.2% and 16.5% for fulvestrant and anastrozole, respectively (although the difference between treatments was not statistically significant). In patients who responded, further follow-up (median, 22.1 months) was performed to obtain more complete information on DOR; the median DOR (from randomization to disease progression) in patients who responded to treatment was 16.7 months in the fulvestrant group and 13.7 months in the anastrozole group. In a statistical analysis of DOR (using all randomized patients; from the start of response to disease progression), DOR was significantly longer for patients in the fulvestrant group compared with patients in the anastrozole group. Both drugs were tolerated well; withdrawals due to drug-related adverse events were 0.9% and 1.2% in the fulvestrant group and the anastrozole group, respectively. The incidence of joint disorders was significantly lower in the fulvestrant group (P = 0.0036),CONCLUSIONS. Fulvestrant was tolerated well and was at least as effective as anastrozole in the second-line treatment of patients with ABC. This new hormonaltherapy may provide a valuable treatment option for ABC in postmenopausal (C) 2003 American Cancer Society.