Toxicity results and early outcome data on a randomized phase II study of docetaxel ± bevacizumab for locally advanced, unresectable breast cancer

3049 Background: Preclinical models of combination angiogenesis inhibitor bevacizumab (rhuMAbVEGF) and docetaxel demonstrate synergistic suppression of capillary vessel formation. Based upon these data, we developed a randomized phase II trial in order to evaluate the vascular effects on tumor regression with combination bevacizumab/docetaxel vs. docetaxel in the treatment of locally advanced breast cancer. Methods: 49 patients (pts) were randomized to receive neoadjuvant therapy with bevacizumab (10 mg/kg qowk) and docetaxel (two 8-week cycles of 35 mg/m 2 weekly x 6 with a 2 wk break) (BD=24) or docetaxel (D=25) alone. Eligible pts had locally unresectable breast cancer with (n=6) or without distant metastasis (n=43); 16 patients presented with inflammatory breast cancer. Pts whose disease responded, sequentially underwent definitive surgery (4 weeks after BD or D), radiation, 4 cycles of conventional Adriamycin/cyclophosphamide, and tamoxifen or anastrazole (if ER/PR+). Results: Among the 49 pts: 7 clinical CRs, 32 PRs, 5 NR, and 5 PD. Of the 37 pts who underwent surgery: the median number of pathologically positive lymph nodes (LN) was 1 (BD=6, D=1; p=0.228); range 0–20; 43% were LN negative. Neoadjuvant treatment toxicity for both arms was acceptable with no significant differences between the two arms. Grade 4 toxicity included BD - new papillary thyroid cancer (1), neutropenia (1), hyperuricemia (1) and colon perforation (1); and D: - hyperglycemia (1) and hyperuricemia (1). 21 patients in each arm experienced a grade 3 toxicity. There were no episodes of uncontrolled hypertension, proteinuria, or thrombosis. Delayed wound healing (unable to start radiation w/in 6 weeks of surgery) occurred in 8 pts: BD=5; D=3 (p=0.691). Only 1 pt (D) experienced a change in LVEF by > 15% or below the institution’s lower limit of normal. Conclusions: Neoadjuvant therapy for locally advanced breast cancer using docetaxel with bevacizumab is well tolerated. Further studies are required to determine the added efficacy from bevacizumab. Correlative studies on impact of treatment on angiogenesis will be reported separately. (Sponsored by grants: K23CA 87725–01, M01 RR 00080, UO1 CA 62502, 5P30 CA43703-NCI/AVON, Aventis) No significant financial relationships to disclose.