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

Abstract

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. 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. 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. 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.