Objective  To mine risk signals for four mesenchymal-epithelial transition factor tyrosine kinase inhibitors (MET-TKIs) using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, and provide reference for the clinical safety of these medications.

Methods  The adverse event (ADE) reports for four MET-TKIs were extracted from the FAERS database using the OpenVigil 2.1 platform, covering data from FDA approval up to July 1, 2024. The data mining was performed using the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) methods. The risk signals were classified and described based on the preferred system organ classification (SOC) and preferred terms (PT) from the International Medical Dictionary (version 23.1).

Results  A total of 2 109, 319, 9 272 and 22 902 ADE reports were identified for 4 MET-TKIs capmatinib, tepotinib, crizotinib and cabozantinib, respectively. After excluding unrelated signals such as product issues, social environment factors, various injuries, poisoning, procedural complications, and medical operations, 63, 41, 64 and 407, positive signals were found, respectively, involving SOCs of 14, 10, 16 and 19. The notable differences were observed in the SOCs affected by the four MET-TKIs. For instance, cabozantinib had more ADE signals related to “skin and subcutaneous tissue disorders”, while crizotinib showed higher occurrences in “eye disorders” compared to the other three MET-TKIs. Similarities among the drugs were noted in “systemic disorders and administration site reactions”, “gastrointestinal disorders”, and “respiratory, thoracic, and mediastinal disorders”. The study also identified ADE not included in the product labeling, such as hearing loss with capmatinib and tepotinib, pulmonary edema with crizotinib, and interstitial lung disease with cabozantinib.

Conclusion  The common ADE signals identified in this study are consistent with those in the product labeling, confirming the reliability of the research methods. Clinicians should monitor ADEs when using these drugs and remain vigilant for ADE signals not mentioned in the product labeling, taking timely preventive measures to ensure the clinical safety.

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