MET Alterations in NSCLC: Amplification, Mutations, and Therapeutic Strategies

In this segment, Dr. Singhi opens by noting that MET nomenclature is already confusing and asks Dr. Jani to walk through what MET-altered NSCLC means. Dr. Jani distinguishes two main facets: MET amplification and MET alterations or mutations. He notes that depending on the type, various TKIs and MET-directed therapies may be utilized. He highlights amivantamab as having dual EGFR/MET receptor blockade but acknowledges that evidence for how to approach cases with co-occurring alterations at baseline remains limited, with evolving data on TKI use at progression and in earlier settings.

Dr. Jani emphasizes the role of the molecular tumor board, particularly when multiple co-mutations are present, such as EGFR plus MET plus TP53. He stresses that molecular tumor boards should not be limited to academic centers, as expanding access is a critical unmet need. He notes these boards include not only thoracic oncologists but also breast and GU oncologists who can contribute cross-disciplinary insights.

Dr. Singhi adds that MET-altered NSCLC encompasses three distinct entities: MET protein overexpression, which may qualify a patient for an antibody-drug conjugate; MET amplification, a common resistance mechanism in EGFR-directed therapy; and MET exon 14 skipping mutations. He underscores that this complexity, compounded by co-alterations, reinforces the need for multidisciplinary collaboration to improve patient outcomes.

In the next episode, "Gaps and Future Directions in NSCLC Biomarker Testing," the panel examines liquid biopsy, MRD, and non-actionable alterations to guide future testing and therapy.