评价来曲唑一线内分泌疗法±贝伐珠单抗用于激素受体阳性进展期乳腺癌绝经后女性的Ⅲ期研究：CALGB 40503
2016年5月2日，美国临床肿瘤学会（ASCO）官方期刊《临床肿瘤学杂志》（JCO）在线发表了纪念斯隆-凯特林癌症中心、达纳-法伯癌症研究所、杜克大学、贝勒医学院、德克萨斯大学MD安德森癌症中心、北卡罗来纳大学教堂山分校、希望之城、加利福尼亚大学旧金山分校、肿瘤学临床试验联盟、印第安纳大学医学院的多中心非盲Ⅲ期研究，调查了抗血管内皮生长因子药物贝伐珠单抗＋来曲唑一线治疗激素受体阳性转移性乳腺癌能否延长无进展生存。
结果发现，贝伐珠单抗＋来曲唑改善了激素受体阳性转移性乳腺癌的无进展生存，但该获益与显著增加的3至4级毒性风险有相关性。识别对贝伐珠单抗治疗有效或耐药的潜在分子标志物的相关研究正在进行中。预测指标研究将澄清贝伐珠单抗在此情况下的作用。
J Clin Oncol. 2016 May 2. [Epub ahead of print]
Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance).
Dickler MN, Barry WT, Cirrincione CT, Ellis MJ, Moynahan ME, Innocenti F, Hurria A, Rugo HS, Lake DE, Hahn O, Schneider BP, Tripathy D, Carey LA, Winer EP, Hudis CA.
Memorial Sloan Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute; Dana-Farber/Partners Cancer Care, Boston, MA; Duke University, Durham, NC; Baylor College of Medicine; The University of Texas MD Anderson Cancer Center, Houston, TX; University of North Carolina at Chapel Hill, Chapel Hill, NC; City of Hope, Duarte; University of California at San Francisco, San Francisco, CA; Alliance for Clinical Trials in Oncology, Chicago, IL; Indiana University School of Medicine, Indianapolis, IN.
PURPOSE: To investigate whether anti-vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor-positive metastatic breast cancer (MBC).
PATIENTS AND METHODS: Women with hormone receptor-positive MBC were randomly assigned 1:1 in a multicenter, open-label, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided α = .025, a target sample size of 352 patients was planned.
RESULTS: From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v 2%) and proteinuria (11% v 0%).
CONCLUSION: The addition of bevacizumab to letrozole improved PFS in hormone receptor-positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting.
PMID: 27138575
PII: JCO661595
DOI: 10.1200/JCO.2015.66.1595