Risk of venous and arterial thromboembolic events associated with VEGFR-TKIs: a meta-analysis

The reported incidence of arterial and venous thromboembolic events varies markedly between VEGFR-TKI-related clinical trials. Here, we performed a meta-analysis to determine the incidence and the relative risk (RR) of venous thromboembolism events (VTEs) and arterial thromboembolic events (ATEs) associated with these agents. Databases (PubMed, Web of Science) were searched for relevant studies. Statistical analyses were conducted to calculate the summary incidences, RRs and 95% confidence intervals (CIs) using either random-effects or fixed-effects models according to the heterogeneity of the included studies. A total of 24,855 patients from 48 studies were included. The overall incidence of all-grade and high-grade VTEs associated with VEGFR-TKIs was 3.6% (95% CI 2.3-5.2%) and 1.6% (95% CI 1.0-2.4%), respectively. The use of VEGFR-TKIs did not significantly increase the risk of developing all-grade (RR 0.91; 95% CI 0.68-1.22; P = 0.558) and high-grade (RR 1.05; 95% CI 0.84-1.31; P = 0.769) VTEs. The overall incidence of all-grade and high-grade ATEs associated with VEGFR-TKIs was 2.7% (95% CI 1.7-3.6%) and 0.6% (95% CI 0.2-1.2%), respectively. The use of VEGFR-TKIs significantly increase the risk of developing all-grade (RR 3.09; 95% CI 1.41-6.76; P = 0.033) ATEs, and a tendency to increase the risk of high-grade (RR 1.49; 95% CI 0.99-2.24; P = 0.101) ATEs was also detected. Patients with cancer that receive VEGFR-TKIs are at high risk of developing ATEs. Physicians should be aware of these adverse effects and should monitor cancer patients receiving VEGFR-TKIs.