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.