Efficacy Evaluation of Bevacizumab Combined with Capecitabine in the Treatment of HER2-Negative Metastatic Breast Cancer: A Meta-Analysis

OBJECTIVE: This study aims to evaluate the efficacy of bevacizumab combined with capecitabine in treating HER2-negative metastatic breast cancer through meta-analysis. METHODS: We searched literature from databases, including PubMed, Web of Science, Wiley Online Library, Ovid, CNKI, and Wanfang databases, for randomized controlled trials (RCTs) of bevacizumab combined with capecitabine (experimental group) and other treatments (control group) for HER2-negative metastatic breast cancer. Retrieved articles were published from the establishment of the database to August 9, 2022. The main outcome indicators were disease progression rate (RDP), disease progression-free survival (PFS), 1-year survival rate (OSR), the occurrence of serious adverse events (SAEs), and objective remission rate (ORR). The risk of bias was assessed according to the Cochrane systematic evaluation tool. Then, the meta-analysis was carried out using Stata16.0 software, and subgroup analysis was carried out based on various intervention methods in the control group. RESULTS: 8 RCTs were finally included in this study, including 2470 patients with HER2-negative metastatic breast cancer. The results of meta-analysis showed that bevacizumab combined with capecitabine had no significant advantage over the control group in terms of RDP, but the results of subgroup analysis were consistent and significant (subgroup 1 (bevacizumab or chemotherapy): DR = −0.03, 95% CI (−0.14, 0.09), P = 0.01; subgroup 2 (bevacizumab plus paclitaxel therapy): DR = −0.03, 95% CI (−0.14, 0.09), P = 0.03). Furthermore, there was no statistical difference in terms of PFS of the experimental group (MD = 9.24, 95% CI (7.88, 32.67), P = 0.05). However, the subgroup analysis showed that the combination of bevacizumab and capecitabine demonstrated a more significant significance than bevacizumab or chemotherapy alone (subgroup 1: MD = 10.11, 95% CI (7.88, 12.34), P = 0.00). Compared with the control group, the experimental group had significant differences in OSR (DR = 0.07, 95% CI (−0.01, 0.15), P = 0.00) and ORR (DR = 0.07, 95% CI (−0.01, 0.15), P = 0.00). In terms of safety, the incidence of serious adverse events in the experimental group did not show a statistically significant difference (MD = 0.01, 95% CI (−0.21, 0.19), P = 0.82). When subgroup analyses were performed, the bevacizumab plus capecitabine regimen was associated with an increased incidence of serious adverse events compared with the drug alone (subgroup 1: MD = 0.02, 95% CI (−0.16, 0.20), P = 0.00) but a reduction in serious adverse events compared with the bevacizumab plus paclitaxel regimen (subgroup 2: DR = −0.01, 95% CI (−0.21, 0.19), P = 0.00). CONCLUSION: The combination therapy of bevacizumab and capecitabine can significantly improve the RDP and OSR of patients compared with the control group. The PFS and ORR of the experimental group are significantly higher than those of bevacizumab or chemotherapy alone. Still, no statistical difference was observed for these outcome indicators between two combined treatments of bevacizumab with capecitabine or paclitaxel. Although this combined treatment scheme may increase the incidence of serious adverse events compared with that of bevacizumab or chemotherapy alone, the incidence of adverse events was decreased compared with bevacizumab combined with paclitaxel. Therefore, the chemotherapy regimen for HER2-negative metastatic breast cancer in clinical practice can be selected according to the actual situation of the patients.