Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer

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Abstract

Neoadjuvant chemotherapy can increase the rates of breast-conserving surgery in patients with operable breast cancer and is a reasonable alternative to adjuvant chemotherapy. Several trials have shown that adding bevacizumab (an antiangiogenic monoclonal antibody against vascular endothelial growth factor A) and the antimetabolites capecitabine and gemcitabine to taxanes can improve outcomes in patients with metastatic breast cancer.

This trial investigated whether adding capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel, followed by doxorubicin plus cyclophosphamide in women with operable human epidermal growth factor receptor 2 (HER2)–negative breast cancer, would increase the rates of pathological complete response in the breast.

The pathological response after the addition of bevacizumab to these neoadjuvant chemotherapy regimens also was investigated; this was the primary end point of this study.

A total of 1206 women with primary operable HER2-negative breast cancer were randomly assigned to 1 of 3 neoadjuvant chemotherapy regimens: (1) docetaxel (100 mg/m2 of body-surface area), administered on day 1 in 4 cycles every 3 weeks, followed by doxorubicin-cyclophosphamide (60 mg and 600 mg/m2, respectively), administered every 3 weeks (docetaxel group); (2) capecitabine (825 mg/m2), administered twice daily on days 1 through 14, added to docetaxel (75 mg/m2), administered on day 1 in 4 cycles, followed by doxorubicin-cyclophosphamide (docetaxel-capecitabine group); or (3) gemcitabine (1000 mg/m2), administered intravenously on days 1 and 8, added to docetaxel (75 mg/m2), administered on day 1 in 4 cycles, followed by treatment with doxorubicin-cyclophosphamide for 4 cycles (docetaxel-gemcitabine group). Patients also were randomized to receive or not receive bevacizumab (15 mg per kg of body weight), administered every 3 weeks, with each of the first 6 cycles of chemotherapy.

Compared with adding docetaxel therapy alone, the addition of capecitabine or gemcitabine did not significantly increase the rate of pathological complete response in the breast (32.7% with docetaxel, 29.7% with docetaxel-capecitabine, and 31.8% with docetaxel-gemcitabine; P = 0.69). Addition of capecitabine or gemcitabine increased toxic effects, specifically, the hand-foot syndrome, neutropenia, and mucositis. Adding bevacizumab was associated with a significant increase in the rate of pathological complete response in the breast (with and without bevacizumab: 34.5 vs 28.2%, respectively; P = 0.02). The greatest benefit of adding bevacizumab was found in the patient subgroup with hormone receptor–positive tumors; there was a weaker effect in the hormone receptor–negative subgroup.

These findings show that the addition of bevacizumab to neoadjuvant chemotherapy is associated with a small but significant increase in the rate of pathological complete response.

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