Summary
MET exon 14 skipping alterations and MET amplifications are recognized as oncogenic and targetable genetic changes in cancer patients. The treatment of MET-selective tyrosine kinase inhibitors (TKIs) in this specific population has shown encouraging therapeutic results. However, a comprehensive understanding of the potential toxicities linked to these agents is still lacking. The present pharmacovigilance analysis was carried out using the FDA Adverse Event Reporting System database to assess notable adverse events associated with MET-selective TKIs. Gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and disturbances in metabolism and nutrition demonstrated a substantial prevalence and significance among the adverse event (AE) categories. Particularly notable were the occurrences of peripheral oedema, nausea, dysphagia, fatigue, and dyspnoea, which emerged as the foremost five reported AEs. The majority of these AEs were observed within the initial months of initiating treatment with MET-selective TKIs and persistently thereafter. Notably, our investigation unveiled a significant correlation between the usage of capmatinib and the incidence of hearing loss and difficulty in swallowing. Diligent monitoring and the implementation of supportive care strategies are essential in managing the toxicities associated with MET-selective TKIs, particularly those related to gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and ototoxicity.
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No datasets were generated or analysed during the current study.
Abbreviations
- AEs :
-
Adverse events
- ROR :
-
Reporting odds ratio
- PRR :
-
Proportional reporting ratio
- IC:
-
Information component
- EBGM :
-
Empirical Bayes Geometric
- HDACs:
-
Mean Histone deacetylases
- FDA:
-
United States Food and Drug Administration
- FAERS :
-
FDA Adverse Event Reporting System
- PT :
-
Preferred term
- SOCs :
-
System organ classes
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Acknowledgements
We appreciate the work of the FAERS database (https://www.fda.gov/).
Funding
This work was supported by the National Natural Science Foundation of China Grant (82373410 to W. Wang).
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Contributions
Wenjie Li: Conceptualization, methodology, data curation, software and writing-review & editing. Wei Wang: Funding acquisition, project administration, supervision and validation. The work reported in the paper has been performed by the authors, unless clearly specified in the text.
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Highlights
• Comprehensive understanding of the potential toxicities linked to MET-selective TKIs is still lacking.
• Gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and disturbances in metabolism and nutrition were prevalent and significant among the adverse event categories.
• Peripheral edema, nausea, dysphagia, fatigue, and dyspnea were the most commonly reported adverse events.
• These adverse events were observed primarily within the initial months of treatment initiation and persisted thereafter.
• Capmatinib usage showed a significant correlation with hearing loss and difficulty in swallowing.
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Li, W., Wang, W. Toxicity burden patterns of MET-selective tyrosine kinase inhibitors: evidence from real-world pharmacovigilance. Invest New Drugs (2024). https://doi.org/10.1007/s10637-024-01437-z
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DOI: https://doi.org/10.1007/s10637-024-01437-z