Bevacizumab in the neoadjuvant treatment of human epidermal growth factor receptor 2-negative breast cancer: A meta-analysis of randomized controlled trials

Several randomized clinical trials have suggested the effectiveness of bevacizumab (Bev) in early and advanced breast cancer; however, due to the increased toxicity and lack of a clear long-term survival benefit, there is currently no defined role for Bev in breast cancer in the USA, while it has been approved in Europe. We herein sought to conduct a meta-analysis of large randomized trials comparing the efficacy and long-term outcome of neoadjuvant chemotherapy with Bev compared with chemotherapy without Bev in human epidermal factor receptor 2 (HER2)-negative breast cancer. A search was conducted through PubMed and Ovid Medline databases. Among the 279 articles identified, 5 met the eligibility criteria and were included in the present analysis. A total of 2,268 patients treated with Bev and 2,278 treated without Bev were analyzed. Pathological complete response (pCR) was obtained in 35% of patients treated with Bev and in 26% of those treated without Bev. A statistically significant increase (26%) in the incidence of pCR was observed in the Bev-treated group. However, patients treated with Bev exhibited no significant difference in the risk of disease recurrence or death. To the best of our knowledge, this is the first meta-analysis addressing the long-term outcomes of Bev in combination with chemotherapy in the neoadjuvant treatment of HER2-negative breast cancer. The results confirmed the significant benefit of Bev combined with chemotherapy compared with chemotherapy alone on breast cancer response, in both triple-negative and hormone receptor-positive cases. However, this benefit does not translate into a long-term disease-free or definitive overall survival advantage. Optimizing patient selection is desirable for maximizing the long-term benefits of Bev, while reducing cost and treatment-related adverse effects. Future efforts directed toward the discovery of predictive markers would be crucial for identifying the subset(s) of breast cancer patients who are most likely to benefit from Bev therapy.