Disproportionality Analysis of Lenvatinib‐Caused Gastrointestinal Perforation in Cancer Patients: A Pharmacovigilance Analysis Based on the US Food and Drug Administration Adverse Event Reporting System

Abstract

Lenvatinib is a medication that targets multiple tyrosine kinases and is commonly used to treat various types of cancer. With its frequent usage, monitoring and assessing its potential adverse effects has become crucial. This study utilizes the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to analyze the possible link between lenvatinib and gastrointestinal perforation. FAERS was used to analyze adverse drug reactions (ADRs) linked with lenvatinib from the first quarter of 2015 to the last quarter of 2022. The association between lenvatinib and gastrointestinal perforation was evaluated using disproportionality analyses. This study included 464 patients who developed gastrointestinal perforation after using lenvatinib. Perforation involved the entire digestive tract, with the colon among the most commonly affected perforation sites, and previously undetected esophageal perforation was frequently observed. Patients with uterine and liver cancer were at a higher risk of developing gastrointestinal perforation; patients with liver cancer experienced a shorter onset time, whereas patients with endometrial cancer had a slower onset time. Middle‐aged and elderly patients exhibited a higher propensity for developing gastrointestinal perforation than younger adults. Patients with gastrointestinal perforation were found to have a significantly higher mortality rate than patients without gastrointestinal perforation. This study has identified several gastrointestinal perforation events not included in the drug instructions. It has also described the perforation site and clinical characteristics based on various types of cancer. These results could provide valuable insights for developing safer and more effective regulatory strategies concerning the use of lenvatinib.