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Updated: Jul 20, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
The Treatment of a New Entity in Advanced Non-small Cell Lung Cancer: MET Exon 14 Skipping Mutation
Danilo Rocco1, Luigi Della Gravara2, Giovanni Palazzolo3
1Department of Pulmonary Oncology, AORN dei Colli Monaldi, Naples, Italy.
Background:
MET (MET Proto-Oncogene, Receptor Tyrosine Kinase) exon 14 skipping mutation represents one of the most common MET alterations, accounting for approximately 1-3% of all mutations in advanced lung adenocarcinomas. While until 2020 no specific treatment was available for this subset of patients, as of today, three MET Tyrosine Kinase Inhibitors (TKIs) are currently approved in this setting, namely capmatinib, tepotinib and savolitinib.
Objective:
This article aims to provide an extensive overview of the current therapeutic standard of care for exon 14 skipped advanced Non-small Cell Lung Cancer (NSCLC) patients, alongside with mentions of the main future challenges and opportunities.
Conclusion:
FDA-approved MET-TKIs currently represent the best option for treating exon 14 skipped advanced NSCLC patients, thanks to their excellent efficacy profile, alongside their manageable safety and tolerability. However, we currently lack specific agents to treat patients progressing on capmatinib or tepotinib, due to a limited understanding of the mechanisms underlying both on- and off-target resistance. In this respect, on-target mutations presently constitute the most explored ones from a mechanistic point of view, and type II MET-TKIs are currently under investigation as the most promising agents capable of overcoming the acquired resistance.
Insights
MET exon 14 skipping mutations in advanced lung cancer are treatable with approved MET Tyrosine Kinase Inhibitors (TKIs). Future research focuses on overcoming resistance to these effective lung cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- MET exon 14 skipping mutations are common in advanced lung adenocarcinomas (1-3%).
- Previously, no targeted treatments existed for this specific mutation.
- Three MET Tyrosine Kinase Inhibitors (TKIs) are now approved: capmatinib, tepotinib, and savolitinib.
Purpose of the Study:
- To review the current standard of care for advanced Non-small Cell Lung Cancer (NSCLC) with MET exon 14 skipping.
- To discuss future challenges and opportunities in treating this patient population.
Main Methods:
- Literature review of current therapeutic standards.
- Analysis of approved MET Tyrosine Kinase Inhibitors (TKIs).
- Discussion of resistance mechanisms and future therapeutic strategies.
Main Results:
- FDA-approved MET-TKIs (capmatinib, tepotinib, savolitinib) are the current standard of care.
- These TKIs demonstrate excellent efficacy with manageable safety profiles.
- Limited agents exist for patients progressing on current therapies due to resistance mechanisms.
Conclusions:
- Current MET-TKIs are the optimal treatment for advanced NSCLC with MET exon 14 skipping.
- Further research is needed to understand and overcome on- and off-target resistance.
- Type II MET-TKIs show promise for treating acquired resistance.
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