MET alterations in NSCLC-Current Perspectives and Future Challenges

Abstract

Targeted therapies have revolutionized the treatment and improved the outcome for oncogene-driven NSCLC and an increasing number of oncogenic driver therapies have become available. For MET-dysregulated NSCLC (especially MET exon 14 skipping mutations and MET-amplifications, which is one of the most common bypass mechanisms of resistance in oncogene-addicted NSCLC), several anti-MET-targeted therapies have been approved recently (MET exon 14 skipping mutation) and multiple others are in development. In this narrative review, we summarize the role of MET as an oncogenic driver in NSCLC, discuss the different testing methods for exon 14 skipping mutations, gene amplification, and protein overexpression, and review the existing data and ongoing clinical trials regarding targeted therapies in MET-altered NSCLC. As immunotherapy with or without chemotherapy has become the standard of care for advanced NSCLC, immunotherapy data for MET-dysregulated NSCLC are put into perspective. Finally, we discuss future challenges in this rapidly evolving landscape.

Keywords: Amivantamab; Capmatinib; MET amplified; MET exon 14; Non–small cell lung cancer; Tepotinib.