Efficacy and Safety of Bevacizumab in Pretreated Metastatic Breast Cancer: A Systematic Review and Meta-Analysis.

Abstract

The use of bevacizumab in patients with previously treated metastatic breast cancer (MBC) is controversial. This meta-analysis was carried out to evaluate the efficacy and safety of the regimen including bevacizumab among patients with pretreated MBC. We systematically searched PubMed, the Cochrane Library, Web of Science, and Embase databases for randomized controlled trials evaluating bevacizumab combined with chemotherapy for previously treated MBC patients. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints were overall survival (OS) and toxicity. The risk of bias was assessed by the Cochrane Collaboration's tool. The pooled hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs) were calculated for the identified studies. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Four studies involving 1,640 individuals were included. Pooling results showed that the PFS of bevacizumab-containing groups (HR 0.82; 95% CI 0.73-0.93, p = 0.002) was significantly better than that of the control groups, especially when bevacizumab was administered as the second-line treatment for patients with human epidermal growth factor receptor 2 (HER2)-negative MBC (HR 0.77; 95% CI 0.66-0.88, p = 0.0002). The ORR in the bevacizumab-containing group was superior to that in the control group, both in the general (RR 1.45; 95% CI 1.18-1.78, p = 0.0004) and HER2-negative groups (RR 1.30; 95% CI 1.03-1.63, p = 0.03). However, no significant effect on OS was demonstrated for the addition of bevacizumab to the second-line treatment for HER2-negative MBC (HR 0.93; 95% CI 0.79-1.10, p = 0.39). Comparatively, proteinuria was more common in the bevacizumab-containing group. In addition, the application of bevacizumab tended to result in therapy discontinuation due to treatment-related toxicity. Bevacizumab-containing chemotherapy, in light of its favorable effects on clinical outcomes, could be a preferred therapeutic option for patients with MBC, for whom the disease must be rapidly relieved. Further studies are warranted for exploring the advantageous patients with the receipt of bevacizumab in multiline treatment.