The efficacy and safety of bevacizumab combined with chemotherapy in treatment of HER2-negative metastatic breast cancer: a meta-analysis based on published phase III trials

Bevacizumab (Bev) combined with chemotherapy significantly improves progression-free survival (PFS) but not overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The efficacy and safety depend on the type of chemotherapy combined with Bev. We performed a meta-analysis of phase III trials to evaluate the efficacy and safety of Bev + standard chemotherapy for HER2-negative MBC. The Cochrane Central Register of Controlled Trials, the Cochrane databases, EMBASE, MEDLINE, and ClinicalTrials.gov were analyzed. The primary outcomes included PFS, OS, and toxicity. Event-based hazard ratios (HRs) and relative risks (RRs) were expressed with the 95 % confidence intervals (CIs). Four randomized controlled trials consisting of 3082 patients were included. Bev + standard chemotherapy improved PFS (HR 0.70, CI 0.64–0.77, P = 0.000) but had no effect on OS (HR 0.92, CI 0.82–1.02, P = 0.119). Bev + chemotherapy increased the incidence of febrile neutropenia (RR 1.45, CI 1.00 to 2.09, P = 0.048), proteinuria (RR 11.68, CI 3.72–36.70, P = 0.000), sensory neuropathy (RR 1.33, CI 1.05–1.70, P = 0.020), and grade ≥3 hypertension (RR 13.94, CI 7.06–27.55, P = 0.000). No differences in efficacy were observed between Bev + paclitaxel and Bev + capecitabine (Cape), but Bev + Cape increased the incidence of neutropenia. Bev + standard chemotherapy improved PFS in HER2-negative MBC patients. No benefit in OS was observed. Bev + Cape and Bev + paclitaxel had similar treatment efficacy, but Bev + Cape had a higher incidence of neutropenia.