Venous thromboembolic events with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A systematic review and meta-analysis of randomized clinical trials

A trial-level meta-analysis was conducted to determine the relative risk (RR) of venous thromboembolic events (VTEs) associated with approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized phase 2 and 3 trials comparing arms with and without a Food and Drug Administration-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, vandetanib, and axitinib). Statistical analyses calculated the RR and 95% confidence intervals (CI), using random-effects or fixed-effects models based on heterogeneity. A total of 7441 patients from 9 phase III trials and 8 phase II trials were selected. The RR of all grade and high-grade VTEs for the TKI vs. no TKI arms was 1.10 (95% CI 0.73-1.66, p=0.64) and 0.85 (95% CI: 0.58-1.25, p=0.41), respectively. No difference in risk was found based on tumor type, age and trial design. The majority of trials exhibited high quality per Jadad scoring and no heterogeneity or publication bias was found.