Real-world safety assessment of MET-targeted therapies: a pharmacovigilance analysis using the FAERS database

Abstract

Background Globally, lung cancer is the foremost contributor to cancer-associated fatalities. Of its various histological sub-types, non-small-cell lung cancer (NSCLC) constitutes the vast majority, accounting for more than 85% of diagnoses. A key driver in this pathology is the mesenchymal–epithelial transition (MET) receptor tyrosine kinase, whose biological activity is governed by the hepatocyte growth factor (HGF) ligand. MET plays a pivotal role in regulating tumour cell proliferation and migration, and aberrant activation of MET signalling is linked to the pathogenesis of NSCLC. Methods A retrospective analysis of the FAERS database (2016–2025) was conducted to obtain adverse event data pertaining to four MET-targeted therapeutic agents, namely amivantamab, savolitinib, capmatinib and tepotinib. A systematic disproportionality analysis was performed to identify adverse events. Results Statistically significant differences were observed across most baseline clinical characteristics. Patients taking tepotinib were significantly older (mean 74.7 years) and experience a higher mortality (21%) than those taking amivantamab, savolitinib or capmatinib. In signal detection, amivantamab caused severe cutaneous/mucosal and infusion-related toxicities. The three c-Met inhibitors led to oedema, with savolitinib distinguished by haematological risks, capmatinib by severe oedema and tepotinib by pulmonary/renal toxicities. In time-to-onset analysis, amivantamab’s infusion-related reaction occurred earliest with the highest incidence; savolitinib (pyrexia/hepatic abnormalities) and capmatinib (nausea) appeared early with relatively high incidences; tepotinib’s peripheral swelling was early but had a low incidence. High death-associated adverse drug reactions included dyspnoea, peripheral oedema, decreased appetite and increased creatinine, warranting further investigation. In cluster analysis, key adverse drug reactions (e.g. infusion-related reactions for amivantamab, hepatotoxicity for savolitinib, peripheral swelling for capmatinib and peripheral oedema for tepotinib) primarily occur as isolated events with limited co-occurrence of multiple toxicities. Conclusion These findings support individualized monitoring and evidence-based treatment selection for older patients, those with comorbidities or patients at high risk with MET-altered NSCLC.