Dickler, Maura N.Barry, William T.Cirrincione, Constance T.Ellis, Matthew J.Moynahan, Mary EllenInnocenti, FedericoHurria, ArtiRugo, Hope S.Lake, Diana E.Hahn, OlwenSchneider, Bryan P.Tripathy, DebasishCarey, Lisa A.Winer, Eric P.Hudis, Clifford A.2018-05-142018-05-142016-08-01Dickler, M. N., Barry, W. T., Cirrincione, C. T., Ellis, M. J., Moynahan, M. E., Innocenti, F., … Hudis, C. A. (2016). 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). Journal of Clinical Oncology, 34(22), 2602–2609. http://doi.org/10.1200/JCO.2015.66.1595https://hdl.handle.net/1805/16159PURPOSE: 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.en-USPublisher PolicyAngiogenesis inhibitorsAntineoplastic agentsAntineoplastic combined chemotherapy protocolsBevacizumabBreast neoplasmsBreast -- CancerArticle