The efficacy and toxicity of anti-VEGFR agents in the treatment of advanced colorectal cancer: a meta-analysis of randomized controlled trials

Aim: The aim of present study was to pool all published data on the efficacy and toxicity of anti-vascular epithelial growth factor receptor (VEGFR) agents in the treatment of advanced colorectal cancer (CRC). Methods: We performed asystematic review of all published studies exploring the efficacy and toxicity of anti-VEGFR agents in advanced CRC patients. The pooled hazard ratio (HR) or relative risk (RR), and 95% confidence intervals (CI) were calculated. Results: Seven randomized controlled trials were included with a total of 4,904 patients. Our results demonstrated that anti-VEGFR agents-containing regimens significantly improved PFS (HR0. 70, 95% CI: 0.55-0.88, P=0.002), but not for ORR (RR1. 29, 95% CI: 0.91-1.83, P=0.151), and OS (HR 0.88, 95% CI: 0.77-1.01, P=0.069). Sub-group analysis according to treatment lines showed that the addition of anti-VEGFR agents to second therapies significantly improved OS, PFS and ORR. However, no significant survival benefits had been observed in anti-VEGFR agents plus first-line treatment for advanced CRC. Additionally, more incidences of grade 3 or 4 hypertension and proteinuria were observed in anti-VEGFR agents-containing regimens, while equivalent frequencies of grade 3 or 4 thrombosis events, GI perforation, congestive heart disease, and hemorrhage were found between the two groups. Conclusions: The findings of this study support the addition of anti-VEGFR agents to second-line therapies in advanced CRC patientsdue to its survival benefits, while no significant survival benefits have been observed in anti-VEGFR agents plus first-line regimens.