Pancreatitis with vascular endothelial growth factor receptor tyrosine kinase inhibitors

Crit Rev Oncol Hematol. 2015 Apr;94(1):136-45. doi: 10.1016/j.critrevonc.2014.11.008. Epub 2014 Dec 4.

Abstract

A trial-level meta-analysis was conducted to determine the relative risk (RR) of pancreatitis associated with multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized phase 2 and 3 trials comparing arms with and without an FDA-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, axitinib, vandetanib, cabozantinib, ponatinib, regorafenib). Statistical analyses calculated the RR and 95% confidence intervals (CI). A total of 10,578 patients from 16 phase III trials and 6 phase II trials were selected. The RR for all grade and high-grade pancreatitis for the TKI vs. no TKI- arms was 1.95 (p=0.042, 95% CI: 1.02 to 3.70) and 1.89 (p=0.069, 95% CI: 0.95 to 373), respectively. No differential impact of malignancy type or specific TKI agent was seen on RR of all grade of high grade pancreatitis. Better patient selection and monitoring may mitigate the risk of severe pancreatitis.

Keywords: Approved; Meta-analysis; Pancreatitis; Tyrosine kinase inhibitors; Vascular endothelial growth factor receptor.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Odds Ratio
  • Pancreatitis / diagnosis
  • Pancreatitis / etiology*
  • Pancreatitis / metabolism
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Randomized Controlled Trials as Topic
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Severity of Illness Index

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Receptors, Vascular Endothelial Growth Factor