Risks and benefits of bevacizumab combined with chemotherapy for advanced or metastatic breast cancer: a meta-analysis of randomized controlled trials

Background: The combination of bevacizumab and chemotherapy has greatly improved progression-free survival (PFS) and objective response rate (ORR) in HER2-negative metastatic breast cancer in many pivotal trials. However, risk–benefit balance related to bevacizumab addition could not be confirmed because of a lack of overall survival (OS) improvement. Therefore, we conducted a meta-analysis to evaluate multiple endpoints pertaining to bevacizumab use in metastatic breast cancer (MBC) treatment. Methods: We searched PubMed and Cochrane Library databases and included seven studies in our meta-analysis in which bevacizumab combined with chemotherapy was compared with chemotherapy alone in MBC. Results: Compared to the chemotherapy-alone group, the combination treatment group had significantly improved PFS [hazard ratio (HR): 0.72, 95% CI 0.67–0.77, P < 0.00001]. Furthermore, bevacizumab addition did not significantly improve OS (HR: 0.95, 95% CI 0.87–1.03, P = 0.22). The ORRs in the combination treatment and chemotherapy-alone groups were 42% and 32%, respectively (HR: 1.47, 95% CI 1.26–1.71, P < 0.00001). Bevacizumab addition significantly increased the incidence of therapy discontinuation due to toxicity and toxicity of grade 3 or higher (HR: 1.43, 95% CI 1.06–1.93, P = 0.02, HR: 1.43; 95% CI 1.25–1.64, P < 0.00001, respectively). A qualitative systematic review of two randomized controlled trials indicated no significant differences in quality of life from baseline between the two groups. Conclusions: Compared to chemotherapy alone, bevacizumab combined with chemotherapy significantly improved PFS in the HER2-negative MBC patients. However, the lack of a significant OS difference remained.