Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer

Abstract

Background Bevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer. The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel, followed by doxorubicin plus cyclophosphamide, would increase the rates of pathological complete response in the breast in women with operable, human epidermal growth factor receptor 2 (HER2)–negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response. Methods We randomly assigned 1206 patients to receive neoadjuvant therapy consisting of docetaxel (100 mg per square meter of body-surface area on day 1), docetaxel (75 mg per square meter on day 1) plus capecitabine (825 mg per square meter twice a day on days 1 to 14), or docetaxel (75 mg per square meter on day 1) plus gemcitabine (1000 mg per square meter on days 1 and 8) for four cycles, with all regimens followed by treatment with doxorubicin–cyclophosphamide for four cycles. Patients were also randomly assigned to receive or not to receive bevacizumab (15 mg per kilogram of body weight) for the first six cycles of chemotherapy. Results The addition of capecitabine or gemcitabine to docetaxel therapy, as compared with docetaxel therapy alone, did not significantly increase the rate of pathological complete response (29.7% and 31.8%, respectively, vs. 32.7%; P = 0.69). Both capecitabine and gemcitabine were associated with increased toxic effects — specifically, the hand–foot syndrome, mucositis, and neutropenia. The addition of bevacizumab significantly increased the rate of pathological complete response (28.2% without bevacizumab vs. 34.5% with bevacizumab, P = 0.02). The effect of bevacizumab on the rate of pathological complete response was not the same in the hormone-receptor–positive and hormone-receptor–negative subgroups. The addition of bevacizumab increased the rates of hypertension, left ventricular systolic dysfunction, the hand–foot syndrome, and mucositis. Conclusions The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response, which was the primary end point of this study. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00408408.)

Sorafenib in the Treatment of Early Breast Cancer: Results of the Neoadjuvant Phase II Study - SOFIA*

“…The pCR rate, defined as no invasive residuals in the breast, was 27.8%, which is comparable to 24.5% (21.9-27.4%) reached with bevacizumab in addition to EC followed by docetaxel in the GeparQuinto study, but slightly lower than 34.5% (30.7-38.3%) in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B40 study [2,3]. The pCR rates, irrespective of the definitions, were slightly above those seen with bevacizumab [2,][3].…”

“…The pCR rates, irrespective of the definitions, were slightly above those seen with bevacizumab [2,][3]. However, the sample size was smaller than initially planned in order to demonstrate an added effect.…”

“…Bevacizumab, an anti-VEGF antibody, has improved progression-free survival of metastatic breast cancer when added to various chemotherapy regimens [1]. In combination with anthracycline/taxane-based chemotherapy given preoperatively, bevacizumab significantly increased the pathological complete response (pCR) rate in early breast cancer [2,3]. …”

Time-dependent pretreatment with bevacuzimab increases tumor specific uptake of cetuximab in preclinical oral cavity cancer studies

“…[19][20][21] However, the mechanism for this improved response remains unclear and the literature surrounding vessel normalization in preclinical models is controversial. Multiple studies have demonstrated evidence of vessel normalization and increased therapeutic uptake.…”

Targeted and Osteo-Oncologic Treatment in Early Breast Cancer: What Is State-of-the-Art and What Might Become so within the Next 5 Years?

“…The phase III GeparQuinto trial reported a significantly higher pCR rate for the combination of chemotherapy and bevacizumab in comparison to chemotherapy alone in this patient subgroup [30]. The NSABP B-40 trial, however, found this effect of bevacizumab predominantly in luminal HR-positive breast cancers [31]. Furthermore, the BEATRICE phase III trial investigated the antibody as an additional treatment to chemotherapy in unselected patients with TNBC, but did not show any benefit in this patient cohort [32].…”