Hepatotoxicity with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis of randomized clinical trials
A partir d'une revue de la littérature (52 essais identifiés, 18 282 patients au total), cette méta-analyse évalue le risque relatif d'une hépatoxicité associée à un traitement par inhibiteur du récepteur VEGFR
A trial-level meta-analysis of randomized phase II/III controlled trials (RCT) was conducted to determine the relative risk (RR) of hepatotoxicity associated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) approved by the U.S. FDA. Citations from PubMed/Medline, abstracts from major conferences, clinicaltrials.gov and manufacturer's package inserts were reviewed to include RCTs comparing arms with or without a VEGFR TKI. The RR of all-grade ALT, AST, ALP and bilirubin elevation in 18,282 patients from 52 trials was 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 elevation was 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. However, the incidence of hepatic failure with VEGFR TKI was only 0.8%. Better post-marketing reporting may modify this calculated risk.
http://www.sciencedirect.com/science/article/pii/S1040842814001930