Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer

Publication

Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer

Journal Paper/Review - Jan 26, 2012

von Minckwitz Gunter, Blohmer Jens-Uwe, Huober Jens, Hauschild Maik, Fehm Tanja, Müller Berit Maria, Denkert Carsten, Loibl Sibylle, Nekljudova Valentina, Untch Michael, German Breast Group, Kunz Georg, Jackisch Christian, Gerber Bernd, Eidtmann Holger, Rezai Mahdi, Fasching Peter A, Tesch Hans, Eggemann Holm, Schrader Iris, Kittel Kornelia, Hanusch Claus, Kreienberg Rolf, Solbach Christine, Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups

Citation

von Minckwitz G, Blohmer J, Huober J, Hauschild M, Fehm T, Müller B, Denkert C, Loibl S, Nekljudova V, Untch M, German Breast Group, Kunz G, Jackisch C, Gerber B, Eidtmann H, Rezai M, Fasching P, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 2012; 366:299-309.

Type

Journal Paper/Review (English)

Journal

N Engl J Med 2012; 366

Publication Date

Jan 26, 2012

Issn Electronic

1533-4406

Pages

299-309

Brief description/objective

BACKGROUND
Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We evaluated the efficacy, measured according to the rate of pathological complete response (absence of invasive and intraductal disease in the breast and the axillary lymph nodes), and the safety of adding bevacizumab to neoadjuvant chemotherapy in patients with early-stage breast cancer.

METHODS
We randomly assigned 1948 patients with a median tumor size of 40 mm on palpation to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, with or without concomitant bevacizumab. Patients with untreated HER2-negative breast cancer were eligible if they had large tumors, hormone-receptor-negative disease, or hormone-receptor-positive disease with palpable nodes or positive findings on sentinel-node biopsy, and no increased cardiovascular or bleeding risk.

RESULTS
Overall, the rates of pathological complete response were 14.9% with epirubicin and cyclophosphamide followed by docetaxel and 18.4% with epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab (odds ratio with addition of bevacizumab, 1.29; 95% confidence interval, 1.02 to 1.65; P=0.04); the corresponding rates of pathological complete response were 27.9% and 39.3% among 663 patients with triple-negative tumors (P=0.003) and 7.8% and 7.7% among 1262 patients with hormone-receptor-positive tumors (P=1.00). Breast-conserving surgery was possible in 66.6% of the patients in both groups. The addition of bevacizumab, as compared with neoadjuvant therapy alone, was associated with a higher incidence of grade 3 or 4 toxic effects (febrile neutropenia, mucositis, the hand-foot syndrome, infection, and hypertension) but with a similar incidence of surgical complications.

CONCLUSIONS
The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome. (Funded by Sanofi-Aventis and Roche, Germany; ClinicalTrials.gov number, NCT00567554.).