LETROZOLE AND BEVACIZUMAB FOR BREAST CANCER

: J Clin Oncol. 2009 Oct 19. [Epub ahead of print]

Related Articles

Feasibility Trial of Letrozole in Combination With Bevacizumab in Patients With Metastatic Breast Cancer.

Traina TA, Rugo HS, Caravelli JF, Patil S, Yeh B, Melisko ME, Park JW, Geneus S, Paulson M, Grothusen J, Seidman AD, Fornier M, Lake D, Dang C, Robson M, Theodoulou M, Flombaum CD, Norton L, Hudis CA, Dickler MN.

Breast Cancer Medicine Service and the Departments of Radiology, Biostatistics, and Renal Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; and University of California San Francisco Comprehensive Cancer Center, San Francisco, CA.

PURPOSE: Preclinical models suggest that the use of anti-vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor-positive metastatic breast cancer (MBC). METHODS: Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease. RESULTS: Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease >/= 24 weeks was noted in 67%. Median PFS was 17.1 months. CONCLUSION: Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).