Hepatotoxicity with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis of randomized clinical trials

A meta-analysis of randomized controlled trials (RCT) was conducted to determine the relative risk (RR) of hepatotoxicity with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Citations from PubMed/Medline, abstracts from major conferences, clinicaltrials.gov and package inserts were reviewed to include RCTs comparing arms with or without a VEGFR TKI. The RRs of all-grade ALT, AST, ALP and bilirubin elevation in 18,282 patients from 52 trials were 1.57 (95% CI 1.38–1.79, p < 0.001), 1.57 (95% CI 1.36–1.81, p < 0.001), 1.20 (95% CI 1.09–1.83, p < 0.001) and 1.55 (95% CI 1.21–1.97, p < 0.001) respectively, and high-grade elevations were 1.66 (95% CI 1.25–2.20, p = 0.001), 1.61 (95% CI 1.21–2.14, p = 0.001), 1.02 (95% CI 0.70–1.47, p = 0.932) and 1.34 (95% CI 1.0–1.81, p = 0.054) respectively compared to those in the non-TKI group. The incidence of hepatic failure with VEGFR TKIs was 0.8%.