Risk of venous and arterial thromboembolic events associated with anti-EGFR agents: a meta-analysis of randomized clinical trials

Anti-epidermal growth factor receptor (EGFR) agents [monoclonal antibodies (MoAbs), tyrosine kinase inhibitors (TKIs)] are targeted therapies used in advanced cancers. Arterial and venous thromboembolic events (ATEs and VTEs excluding catheter-related events) were not investigated with these agents, and the risk of these events is still unknown. We have carried out a meta-analysis in order to determine the incidence and the relative risk (RR) of VTEs and ATEs associated with these agents. Statistical analyses were conducted to calculate the summary incidence, RRs and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of the included studies. A total of 13 studies (7611 patients) was selected for this meta-analysis. The associated RRs of VTEs (11 studies comprising 7073 patients) and ATEs (5 studies consisting of 3030 patients) were 1.32 (95% CI 1.07-1.63; P equals 0.01) and 1.34 (95% CI 0.94-1.9; P equals 0.11) compared with control patients. The analysis of VTEs was also stratified by class of agents: MoAbs (RR 1.34; P equals 0.01) and oral TKIs (RR 1.16; P equals 0.65). Anti-EGFR agents are associated with a significant increase in the risk of VTEs. In particular, the risk is significant with cetuximab and panitumumab in settings where these drugs are currently approved.