Comparative Toxicovigilance of Capmatinib and Tepotinib in NSCLC: Respiratory Signal Detection and Adverse Event Profiling via FAERS

Capmatinib and tepotinib are selective MET inhibitors for MET exon 14 skipping non-small cell lung cancer (NSCLC), yet comprehensive real-world safety profiles, particularly concerning respiratory and rare adverse events (AEs), remain limited. We conducted a disproportionality analysis of the FDA AE Reporting System (FAERS) database, utilizing four algorithms (ROR, PRR, BCPNN, MGPS) to identify AE signals from 1771 cases for capmatinib and 470 for tepotinib, standardized with MedDRA v26.0. Both inhibitors shared signals for systemic AEs, such as peripheral oedema and gastrointestinal disorders. However, their respiratory AE profiles diverged: capmatinib was associated with pleural effusion and pulmonary oedema, whereas tepotinib was linked to infectious complications, including interstitial lung disease and infectious pleural effusion. Importantly, we identified significant novel signals beyond current drug labels: sensory disturbances, and thrombosis for capmatinib; and fluid imbalance-related events for tepotinib. These distinct AE profiles highlight an infection-driven pulmonary risk for tepotinib requiring close monitoring, while capmatinib's association with sensory disorders warrants specific patient management considerations. Our findings underscore the need for individualized safety monitoring based on the unique AE profiles of each MET inhibitor.