Optimizing the treatment of bevacizumab as first-line therapy for human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer: an updated meta-analysis of published randomized trials

BACKGROUND Manifold data have demonstrated that the addition of bevacizumab to chemotherapy improved progression-free survival (PFS), while few trials have revealed its significant overall survival (OS) benefit. Furthermore, it still remains suspended how to maximize the benefits of bevacizumab as first-line therapy for human epidermal growth factor receptor 2 (HER2)-negative breast cancer. We sought to conduct a meta-analysis to assess the benefits of bevacizumab with chemotherapy and to identify the ideal chemotherapy partner of bevacizumab in the first-line setting for HER2-negative advanced breast cancer patients. METHODS Computerized and manual searches were performed to identify randomized clinical trials evaluating the efficacy of bevacizumab plus chemotherapy versus chemotherapy alone or bevacizumab with different chemotherapy regimens as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer patients. Risk ratios or odds ratios with their 95% CIs were used to estimate the association between multiple combinations of bevacizumab with chemotherapy and various clinical outcomes. RESULTS With 7 trials identified, this analysis included 3,984 eligible patients. The addition of bevacizumab to chemotherapy resulted in a statistically significant improvement in PFS (P=0.019) and objective response rate (ORR; P<0.001) rather than in OS (P=0.783) when compared with chemotherapy alone. The greater benefits in PFS and ORR were achieved from bevacizumab plus taxane-based regimens compared with bevacizumab plus capecitabine-based regimens, while bevacizumab plus capecitabine had comparable OS with bevacizumab plus paclitaxel. Additionally, bevacizumab-based triplet therapy failed to improve the clinical outcomes when compared with doublet therapy. CONCLUSION This meta-analysis reveals that the addition of bevacizumab to chemotherapy yielded PFS and ORR benefits in HER2-negative advanced breast cancer. Additional studies are still prompted to further optimize the first-line treatment of bevacizumab.