Letrozole (L) with bevacizumab (B) is feasible in patients (pts) with hormone receptor-positive metastatic breast cancer (MBC)

3050 Background: Bevacizumab added to chemotherapy (CRx) prolongs PFS in pts with MBC. Data suggest that estrogen (E2) modulates VEGF-induced angiogenesis in physiologic and pathologic conditions. E2-induced VEGF expression may promote breast cancer growth therefore combination therapy with an aromatase inhibitor (AI) and an antibody to VEGF may be more effective than either agent alone. We performed a feasibility study testing B with L for the treatment (tx) of hormone receptor-positive MBC. Methods: Eligible pts have MBC and are candidates for AI therapy. Prior non-steroidal AI (NSAI) use without progression is permitted. Premenopausal pts undergo ovarian suppression/oophorectomy prior to tx. Therapy consists of L (2.5 mg daily) and B (15 mg/kg IV q3 weeks). The primary endpoint is frequency of Grade (Gr) 4 toxicity. Secondary endpoints include response rate, stable disease (SD) ≥ 6 mo and time to tumor progression. Using a two-stage design, 19 pts were accrued. Because <3 pts had Gr 4 toxicity, the 2nd stage is now enrolling an additional 23 pts. If <5 of the 42 pts have Gr 4 toxicity, the regimen will be considered feasible. Results: Thirty two pts are currently accrued and 28 are now evaluable. Medians: Age 49.5 yrs (32–77) and ECOG PS 0 (0–1). Sites of MBC: bone only 11/28, visceral 16/28, chest wall/soft tissue/lymph nodes 11/28. All are ER and/or PR (+); none are HER2 (+). Prior therapy: adjuvant CRx 20; adjuvant tamoxifen 14. Twenty five pts received an NSAI as first-line tx of MBC, starting a median of 23 wks (1–213) before B. Three pts received first-line tamoxifen; one pt had prior CRx for MBC. After a median of 8 cycles (1–20), tx-related toxicities: Gr 2: hypertension (HTN) 4, headache (HA) 4, proteinuria 3, fatigue 6, joint pain 5, hot flashes 1, epistaxis 1; Gr 3: HTN 5, HA 1, proteinuria 1. There has been no tx-related Gr 4/5 toxicity. Tx-related withdrawals: HTN 1 and headache 1. Twenty five pts are evaluable for response: PR 2, SD ≥ 6 mo 13, SD 4, progression 6. Conclusions: Combination L and B is well tolerated and will be studied in a randomized CALGB trial. Circulating endothelial and tumor cell data is reported separately. Supported in part by Genentech and Novartis. [Table: see text]