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Absence of cross-toxicity between MET inhibitors in a non-small-cell lung cancer with a MET exon 14 skipping mutation
Ariane Vanderick1, Benoît Colinet2
1Pneumology, Université catholique de Louvain (UCL), Brussels, Belgium.
Introduction:
Selective tyrosine kinase inhibitors are proven effective in patients with non-small lung cancer (NSCLC) with a MET exon 14 skipping mutation.
Case Presentation:
The patient developed a metastatic lung adenocarcinoma with a MET exon 14 skipping mutation. She was treated with a first 1b MET inhibitor, Capmatinib, but had to stop the drug because of major hepatotoxicity. A few months later, she started Tepotinib, another 1b MET inhibitor with this time, no sign of hepatotoxicity.
Discussion:
Adverse events are frequent with 1b MET inhibitors. However, there is a wide interpatient variability. Absence of cross-toxicity between Capmatinib and Tepotinib is misunderstood but can be explained by slight differences in phamarcodynamics and pharmacokinetics. Practitionners have to be warned about severe adverse events to stop or change the drug if necessary.
Conclusion:
This is the first case showing the absence of cross-toxicity between 1b MET inhibitors.
Insights
Selective tyrosine kinase inhibitors, like Capmatinib and Tepotinib, are effective for non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations. This case highlights no cross-toxicity between these MET inhibitors, despite initial Capmatinib-induced hepatotoxicity.
Area of Science:
- Oncology
- Pharmacology
Background:
- Selective tyrosine kinase inhibitors targeting MET exon 14 skipping mutations are established treatments for non-small cell lung cancer (NSCLC).
- MET inhibitors, particularly type 1b, are associated with potential adverse events, necessitating careful patient monitoring.
Observation:
- A patient with metastatic lung adenocarcinoma and a MET exon 14 skipping mutation experienced severe hepatotoxicity while on Capmatinib, a type 1b MET inhibitor.
- Following discontinuation of Capmatinib, the patient was successfully treated with Tepotinib, another type 1b MET inhibitor, without recurrence of hepatotoxicity.
Findings:
- This case presents the first documented instance of absent cross-toxicity between Capmatinib and Tepotinib in a patient with NSCLC.
- The observed lack of cross-toxicity may be attributed to subtle differences in the pharmacodynamics and pharmacokinetics of these two MET inhibitors.
Implications:
- Clinicians should be aware of the potential for varying toxicity profiles among MET inhibitors, even within the same class.
- The absence of cross-toxicity suggests that patients who experience severe adverse events with one MET inhibitor may tolerate another, offering alternative treatment options.
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