阿那曲唑+氟维司群可延长乳腺癌患者生存

8月2日《新英格兰医学杂志》发表的美国西南肿瘤协作组(SWOG)S0226 试验结果显示，阿那曲唑(瑞宁得)+氟维司群(芙仕得)联合用药方案可使初治的激素受体阳性转移性乳腺癌绝经后女性患者生命延长6个月(N. Engl. J. Med. 2012; 367: 435-4 [doi: 10.1056/NEJMoa1201622])。

加州大学欧文分校医学中心的Rita S. Mehta博士及其同事报告称，单纯阿那曲唑治疗组中位总生存期为41.3个月，而阿那曲唑+氟维司群联合治疗组为47.7个月。联合治疗组的生存优势还表现在，尽管41%的对照组患者在疾病进展后改为氟维司群单药治疗，联合治疗组的死亡风险仍明显降低(HR，0.81)。中位无进展生存期(主要终点指标)也呈统计学显著性改善(13.5个月vs.15个月)。虽然3例死亡患者可能与联合用药治疗有关，但3~5级不良事件未见组间显著差异。

该项研究入组707例患者，其中694例纳入意向治疗分析。所有受试者均每天口服1 mg阿那曲唑，试验组还在第1天肌注500 mg负荷剂量的氟维司群，在第14和28天以及此后每28天给予250 mg的氟维司群。该剂量小于美国食品药品管理局(FDA)批准的500 mg剂量， 2011年2月2日修订后的方案允许两组患者在出现疾病进展后接受更大剂量的氟维司群治疗。

该研究由美国国立癌症研究所和阿斯利康公司资助，作者相关利益披露信息详见www.nejm.com。

研究者曾在2011年12月召开的圣安东尼奥乳腺癌研讨会上报告了部分研究结果，爱思唯尔出版物《肿瘤学报道》副主编Hope Rugo 博士和 William Gradishar博士在会议期间对该治疗方案的讨论视频链接如下：http://youtu.be/hKh8yrr6BGY。

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By: JANE SALODOF MACNEIL, Ob.Gyn. News Digital Network

A regimen combining anastrozole with fulvestrant added 6 months to the lives of postmenopausal women with previously untreated, hormone receptor–positive metastatic breast cancer, according to clinical trial results published August 2 in the New England Journal of Medicine.

Overall survival increased significantly from a median of 41.3 months with anastrozole (Arimidex) alone to 47.7 months with anastrozole and fulvestrant (Faslodex) in the Southwest Oncology Group (SWOG) S0226 trial. The combination’s survival advantage prevailed with a hazard ratio for death of 0.81 despite crossover to single-agent fulvestrant by 41% of patients in the control group after disease progression.

Median progression-free survival, the trial’s primary end point, also showed a statistically significant improvement from 13.5 months to 15 months, Dr. Rita S. Mehta of the University of California, Irvine, Medical Center, and her associates report (N. Engl. J. Med. 2012; 367: 435-4 [doi: 10.1056/NEJMoa1201622]).

The study randomized 707 patients, of whom 694 were included in the intention-to-treat analysis. All participants received 1 mg of anastrozole orally each day. Those assigned to the experimental arm also received a 500 mg loading dose of fulvestrant administered intramuscularly on day 1, followed by 250 mg on days 14 and 28 of 28-day cycles. The fulvestrant dose is lower than the 500-mg dose approved by the Food and Drug Administration, and the protocol was amended on Feb. 2, 2011 to allow patients in both study arms to receive the higher dose upon progression.*

Although three deaths may have been associated with the combination treatment, the investigators report that grade 3-5 adverse events were not significantly different between the two arms of the trial.

The study was funded by the National Cancer Institute and AstraZeneca. Disclosures for the individual authors are posted at www.nejm.com.

The NEJM report expands on results presented at the San Antonio Breast Cancer Symposium in December 2012. Dr. Hope Rugo and Dr. William Gradishar, associate editors of The Oncology Report, a publication of Elsevier, discussed the regimen at that meeting in this accompanying video: