Adverse event signal analysis of type Ib MET tyrosine kinase inhibitors based on food and drug administration adverse event reporting system.

Abstract

Background: Type Ib MET Tyrosine Kinase Inhibitors (TKIs), such as capmatinib, tepotinib, and savolitinib, are used to treat MET-amplified and MET exon 14 deletion mutant non-small cell lung cancer. This pharmacovigilance study analyzed data from the FDA Adverse Event Reporting System (FAERS) between September 2014 and March 2024 to assess adverse events (AEs) for these FDA-approved drugs.

Research design and methods: We conducted a systematic search of AEs using MedDRA SMQs by SOC and PT, and performed disproportionality analysis to identify safety signals, calculating ROR, PRR, EBGM, and IC.

Results: The analysis identified significant safety signals: capmatinib showed signals for ear and labyrinth disorders, neoplasms, general disorders, and hepatobiliary disorders; tepotinib for renal and urinary disorders, ear and labyrinth disorders, metabolism and nutrition disorders, and general disorders; savolitinib for hepatobiliary disorders. Key PT signals included protein deficiency, scrotal edema, and chylothorax for capmatinib; edema and decreased blood albumin for tepotinib; and abnormal hepatic function for savolitinib.

Conclusion: The study highlights differences in the safety profiles of Type Ib MET TKIs, underscoring the need for further regulatory review and possible updates to product labels to better inform clinicians and patients.