Neoadjuvant Chemotherapy and Bevacizumab for HER2-Negative Breast Cancer

When neoadjuvant chemotherapy agents (anthracyclines, taxanes, and agents directed against antihuman epidermal growth factor receptor 2 [HER2], if indicated), are used, approximately 30% to 40% of all breast cancers that are HER2-positive or triple-negative (estrogen-receptor–negative, progesterone-receptor–negative, and no overexpression of HER2) are completely eradicated locally at the time of surgery. The GeparQuinto phase 3 study was initiated to investigate subtype-specific treatment approaches for patients with HER2-negative primary breast cancer (group 1), HER2-negative primary breast cancer that did not have a response to 4 cycles of neoadjuvant chemotherapy as confirmed by ultrasonography (group 2), or HER2-positive primary breast cancer (group 3). The researchers reported results in the New England Journal of Medicine [2012;366(4):299-309]. The report focused on patients in group 1—those with HER2-negative, operable or locally advanced tumors who were treated with anthracycline- and taxane-based neoadjuvant chemotherapy. The patients were randomly assigned to either simultaneous treatment with bevacizumab or no additional therapy. The primary objective of the HER2-negative component of the study was to compare the rates of pathologic complete response after neoadjuvant chemotherapy with or without bevacizumab among patients with HER2-negative primary breast cancer. The secondary end points included toxic effects, adherence to treatment, the response rates of breast tumors and axillary nodes as assessed by physical examination and imaging tests (ultrasonography, mammography, or magnetic resonance imaging) before surgery, the rates of pathologic stage T0 and Tis tumors (with “is” denoting in situ and referring to residual intraductal disease) after neoadjuvant therapy irrespective of nodal status, the rate of pathologic stage T0 or TisN0 (no invasive residual disease in the breast and lymph nodes) tumors after neoadjuvant therapy, and the rate of breast conservation. Efficacy was assessed in predefined subgroups according to tumor stage. A total of 1948 patients with untreated HER2-negative breast cancer from 126 centers in Germany and 1 in Switzerland were randomized to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, with or without concomitant bevacizumab. Patients had a median tumor size of 40 mm on palpation. Eligible patients had large tumors, hormone-receptor–negative disease, hormone-receptor–positive disease with palpable nodes or positive findings on sentinel-node biopsy, as well as no increased cardiovascular or bleeding risk. A total of 144 patients who received epirubicin and cyclophosphamide followed by docetaxel (14.9%) and 176 patients treated with epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab (18.4%) had a pathologic complete response (pathologic stage T0N0) (odds ratio [OR] with the addition of bevacizumab, 1.29; 95% confidence interval [CI], 1.02-1.65; P=.04). After adjustment for age, clinical tumor and nodal stage, hormone-receptor status, tumor grade, and histologic type as covariates, OR with the addition of bevacizumab was 1.36 (95% CI, 1.05-1.77; P=.02). Among 663 patients with triple-negative tumors, the rates of pathologic complete response were 27.9% in the group that received epirubicin and cyclophosphamide followed by docetaxel and 39.3% in the group that received epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab (P=.003), and among 1262 patients with hormone-receptor–positive tumors, the corresponding rates were 7.8% and 7.7%. The overall clinical response rate, determined by means of palpation and imaging tests, was higher in the group that received bevacizumab than in the group that did not (87.4% vs 79.6%). A total of 66.6% of patients in both groups had breast-conserving surgery.