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Randomized Controlled Trial
. 2012 Jan 26;366(4):310-20.
doi: 10.1056/NEJMoa1111097.

Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer

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Free PMC article
Randomized Controlled Trial

Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer

Harry D Bear et al. N Engl J Med. .
Free PMC article

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.).

Figures

Figure 1
Figure 1. Pathological Complete Response (pCR)
The percentages of patients with pCR in the breast (Panel A) and in the breast and nodes (Panel B) are shown according to chemotherapy regimen (docetaxel followed by doxorubicin–cyclophosphamide [T–AC], docetaxel and capecitabine followed by doxorubicin–cyclophosphamide [TX–AC], or docetaxel and gemcitabine followed by doxorubicin–cyclophosphamide [TG–AC]). In addition, the percentages of patients with pCR in the breast (Panel C) and in the breast and nodes (Panel D) are shown according to receipt or no receipt of bevacizumab.
Figure 2
Figure 2. Subgroup Analyses of the Effect of Bevacizumab on Pathological Complete Response (pCR)
The effect of bevacizumab with respect to pCR in the breast (Panel A) and in the breast and nodes (Panel B) is shown across various subgroups of eligible patients. P values were calculated from tests for the homogeneity of the effects of bevacizumab across patient subgroups.

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