Phase II multicenter study of docetaxel and bevacizumab with or without trastuzumab as first-line treatment for patients with metastatic breast cancer.

BACKGROUND: Adding bevacizumab to docetaxel or paclitaxel in the first-line improves the progression-free survival (PFS) of metastatic breast cancer (MBC) patients. Docetaxel has been studied with bevacizumab at the maximally tolerated dose of 100 mg/m(2). We investigated the effects of combining bevacizumab with docetaxel (75 mg/m(2)) with or without trastuzumab for human epidermal growth factor receptor 2-positive (HER2(+)) and HER2-negative (HER2(-)) patients, respectively.

PATIENTS AND METHODS: We conducted a phase II study, stratified by HER2 status, of patients with locally advanced breast cancer or MBC who had received no prior chemotherapy for metastatic disease and showed no evidence or history of central nervous system metastases. Stratum 1 (HER2(-)) treatment consisted of bevacizumab (15 mg/kg) followed by docetaxel (75 mg/m(2)) administered every 3 weeks; stratum 2 (HER2(+)) treatment was the same as that of stratum 1 with the addition of trastuzumab (8 mg/kg loading dose on day 2 of cycle 1, and 6 mg/kg on day 1 of all subsequent cycles).

RESULTS: The trial accrued 73 patients (stratum 1, 52 patients; stratum 2, 21 patients). The most common grade 3 or 4 adverse event (all strata) was fatigue (stratum 1, 11.5%; stratum 2, 10%). The incidence of grade 3 hypertension was 6% for stratum 1 and 5% for stratum 2. The median PFS was 8.4 months (95% CI, 5.2-10.4 months) in stratum 1; the median PFS in stratum 2 was 13.3 months (95% CI, 11.9-35.4 months). The overall response rate for stratum 1was 58% and for stratum 2 was 81%, and the clinical benefit rates were 67% and 81%, respectively.

CONCLUSION: In first-line treatment of MBC, adding docetaxel (75 mg/m(2)) to bevacizumab administered every 3 weeks in HER2(-) patients, and docetaxel plus trastuzumab plus bevacizumab treatment in HER2(+) patients are feasible and safe, with high response rates and promising PFS compared with those of bevacizumab-naive historic controls.