Bevacizumab Combined with Chemotherapy as First-line Therapy for Metastatic Colorectal Cancer: A Meta-analysis

Objective To assess the efficacy and safety of bevacizumab(BEV) combined with chemotherapy as a first-line therapy for metastatic colorectal cancer(mCRC). Methods A wide search of randomized clinical trials using BEV combined with chemotherapy as a first-line therapy for mCRC patients was performed in the Cochrane Library，PubMed，EmBase and CBM，CNKI，VIP，WanFang databases. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were objective response rate (ORR) and toxicity. Relative risk (RR) and hazard ratios (HR) were expressed by 95% confidence intervals (95%CI). The software Stata 11.0 was used for meta-analysis. Results We involved 9 RCT trials, totally 3930 patients. Meta analysis indicated that compared with chemotherapy alone, BEV combined with chemotherapy could decrease the risk of progressive disease（HR=0.62, P<0.0001, 95%CI: 0.64-0.74）and the risk of disease death（HR=0.84, P<0.001, 95%CI: 0.73-0.95）, and could increase the ORR of mCRC patients（RR=0.80, P<0.001, 95%CI: 0.60-0.93）. Subgroup analysis indicated that the combination of BEV and double therapy could decrease the risk of progressive disease（HR=0.68, P<0.001, 95%CI: 0.46-0.89），but no decrease in the risk of disease death(HR=0.85, P=0.068, 95%CI: 0.68-1.03). The combination of BEV and monotherapy could decrease the risk of progressive disease(HR=0.56, P<0.001, 95%CI: 0.47-0.64) and the risk of disease death(HR=0.83, P<0.001, 95%CI: 0.68-0.97). Regarding the toxicity, BEV combined with chemotherapy didn't increase the treatment-related mortality(RR=0.97, P=0.91, 95%CI: 0.62-1.54), but increased the rates of BEV-associated adverse effects. Conclusion BEV combined with chemotherapy as a first-line treatment could increase the PFS,OS and ORR of mCRC patients. The benefit was dissimilar between BEV with monotherapy and BEV with double therapy. Although the BEVassociated adverse effect was increased, they could be controlled.