Adding Bevacizumab to Neoadjuvant Chemotherapy Increases Complete Response Rates
Findings from 2 separate studies have shown that adding the vascular endothelial growth factor inhibitor bevacizumab to adjuvant chemotherapy regimens improves response rates in patients with early-stage breast cancer (Bear HD, et al. N Engl J Med. 2012;366:310-320; von Minckwitz G, et al. N Engl J Med. 2012;366:299-309). In the first study, 1206 women with primary operable HER2-negative breast cancer were randomized to receive docetaxel, alone or in combination with capecitabine or gemcitabine, every 3 weeks, followed by doxorubicin plus cyclophosphamide every 3 weeks, for 4 cycles. In addition, 604 of these patients also received bevacizumab with each of the first 6 chemotherapy cycles. The primary end point was the pathologic complete response (pCR). In the German Breast Group study, 1948 women with untreated HER2-negative breast cancer were randomized to receive neoadjuvant epirubicin and cyclophosphamide every 3 weeks, followed by docetaxel every 3 weeks, for 4 cycles. Half of this group also received bevacizumab for 8 cycles, beginning with the first cycle of epirubicin and cyclophosphamide.
In the first study, 59% of the tumors were hormone receptor (HR)-positive. Among 1186 evaluable patients, the addition of capecitabine or gemcitabine to docetaxel therapy did not increase the pCR rate over docetaxel alone, but both were associated with increased toxicities. Compared with patients who did not receive bevacizumab, however, those who received bevacizumab had significant improvement in pCR in the breast (28.2% vs 34.5%, respectively) but not in the breast and nodes. The pCR with bevacizumab was more pronounced in women with HR-positive tumors (23.2% vs 15.1%, respectively).
In the second study, a similar overall benefit of bevacizumab was demonstrated. The pCR was greater in patients who received bevacizumab than in those who did not (18.4% vs 14.9%, respectively). However, the benefit of bevacizumab was significantly greater only in patients with triple-negative tumors (39.3% vs 27.9%, respectively), not in those with HR-positive tumors. The improvement in the pCR rate implies that more women would be spared primary surgery for their breast cancer. In both groups, pCR was higher in the bevacizumab group. However, it is unclear whether this increased response will translate into prolonged survival.