Pancreatitis with vascular endothelial growth factor receptor tyrosine kinase inhibitors

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are crucial in cancer therapy.
• Pancreatitis is a known adverse event associated with TKIs.
• Quantifying the precise risk of pancreatitis across various VEGFR TKIs is essential for clinical management.

Purpose of the Study:

• To conduct a trial-level meta-analysis assessing the relative risk (RR) of pancreatitis in patients treated with multi-targeted VEGFR TKIs.
• To compare the incidence of all-grade and high-grade pancreatitis between VEGFR TKI arms and control arms in clinical trials.

Main Methods:

• A systematic literature search identified eligible randomized phase 2 and 3 trials.
• Data from 10,578 patients across 22 trials comparing FDA-approved VEGFR TKIs (e.g., sunitinib, sorafenib) with control arms were analyzed.
• Statistical analyses calculated the RR and 95% confidence intervals (CI) for pancreatitis incidence.

Main Results:

• The overall relative risk for all-grade pancreatitis was 1.95 (p=0.042), indicating a significant increase in risk with VEGFR TKI use.
• The relative risk for high-grade pancreatitis was 1.89 (p=0.069), suggesting a trend towards increased severe pancreatitis.
• No significant differences in pancreatitis risk were observed based on malignancy type or specific TKI agent.

Conclusions:

• Multi-targeted VEGFR TKIs are associated with a nearly twofold increased risk of developing pancreatitis.
• While the risk of high-grade pancreatitis did not reach statistical significance, a concerning trend was observed.
• Enhanced patient selection and vigilant monitoring are crucial to mitigate the risk of severe pancreatitis in patients receiving VEGFR TKIs.