In a new study from von Minckwitz et al, bevacizumab added to neoadjuvant combination chemotherapy increased the rate of pathological complete response among patients with HER-2-negative early-stage breast cancer. The effect was greatest in patients with the poorest prognosis, those with so-called triple-negative tumors.
The efficacy of neoadjuvant chemotherapy, as measured by the rate of pathological complete response (the absence of disease in the breast and the axillary lymph nodes), varies according to breast-cancer subtype. When anthracyclines, taxanes, and agents directed against anti-human epidermal growth factor receptor 2 (HER2) are used, approximately 30 to 40% of all breast cancers that are HER2-positive or triple-negative (estrogen-receptor-negative, progesterone- eceptor-negative, and no overexpression of HER2) are completely eradicated locally at the time of surgery. Long-term follow-up studies have shown a consistent correlation between pathological complete response and low rates of relapse and death among patients with these two subtypes of breast cancer.
• What is the mechanism of action of bevacizumab?
Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor A (VEGF). It inhibits the interaction between VEGF and receptors on the surface of endothelial cells, thus preventing their proliferation and inhibiting the formation of new blood vessels. Bevacizumab has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer.
• What are the benefits of adding bevacizumab to anthracycline and taxane containing chemotherapy in HER2-negative early-stage breast cancer?
In this week’s issue of the Journal, the addition of bevacizumab to neoadjuvant chemotherapy was found to significantly increase 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. 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 pathological complete response (pathological stage T0N0) (odds ratio with the addition of bevacizumab, 1.29; 95% confidence interval, 1.02 to 1.65; P=0.04).
Morning Report Questions
Q: What side effects were associated with the use of bevacizumab?
A: Bevacizumab-specific toxic effects, such as bleeding and arterial hypertension, occurred more frequently in the group that received bevacizumab than in the group that did not. Similar to results from previous studies, the authors observed an increased incidence of toxic effects typically associated with docetaxel in the group that received bevacizumab. The addition of bevacizumab to epirubicin and cyclophosphamide followed by docetaxel was associated with a higher rate of febrile neutropenia, infections, mucositis, and the hand-foot syndrome. A protective effect of bevacizumab on chemotherapy-induced edema has been described.
Q: Was there a difference between groups in breast-conserving therapy or mortality?
A: The rate of breast-conserving surgery was identical (66.6%) in both treatment groups. Patients were considered to have had breast-conserving surgery if the final surgical procedure was tumorectomy, segmentectomy, or quadrantectomy. Because of the short follow-up period, the authors could not determine if the observed increases in the rate of pathological complete response translated into a survival advantage.