Adverse events risk associated with anti-VEGFR agents in the treatment of advanced nonsmall-cell lung cancer: A meta-analysis

Abstract

To perform this meta-analysis, we investigated the risk of the most clinically relevant adverse events related to antivascular endothelial growth factor receptor (VEGFR) agents in advanced nonsmall-cell lung cancer (NSCLC). A comprehensive literature search for studies published up to October 2015 was performed. Prospective randomized controlled phase II/III clinical trials that comparing therapy with or without anti-VEGFR agents for advanced NSCLC were included for analysis. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using random effects or fixed effects according to the heterogeneity among included trials. A total of 11,701 patients from 18 clinical trials were included for analysis. Pooled RR showed that the use of anti-VEGFR agents significantly increased the risk of developing hypertension (RR 4.71, 95% CI 3.29-6.73, P<0.001) and fatal adverse events (RR 1.33, 95% CI 1.12-1.58, P=0.001). No statistically significant differences were found for gastrointestinal (GI) perforation (P=0.41), arterial or venous thromboembolic events (P=0.49 and P=0.16, respectively), or hemorrhagic events (P=0.81). Sensitive analysis indicated that the significance estimate of pooled RR of fatal adverse event (FAEs) was not significantly influenced by omitting any single study. The use of anti-VEGFR agents in advanced NSCLC does significantly increase the risk of hypertension and fatal adverse events, but not for arterial or venous thromboembolic events, GI perforation, or hemorrhagic events. Abbreviations: AEs = adverse events; ATEs = arterial thromboembolic events; CIs = confidence intervals; FAEs = fatal adverse event; GI = gastrointestinal; NSCLC = non-small-cell lung cancer; ORR = objective response rate; PFS = progression-free survival; RR = relative risk; VEGFR = vascular endothelial growth factor receptor; VTEs = venous thromboembolic events.