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

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.

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.

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.

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.