Metastatic NSCLC — MET Exon 14 Skipping

Sequencing for MET exon 14 skipping metastatic non-small cell lung cancer: a MET-directed tyrosine kinase inhibitor (capmatinib or tepotinib) first line, then platinum-pemetrexed chemotherapy with or without immunotherapy on progression.

1L: MET inhibitor (capmatinib or tepotinib)

Preferred first-line targeted therapy; deepest responses occur in treatment-naive patients, and MET TKIs remain active if the alteration is identified after prior chemotherapy. Monitor peripheral edema, nausea, and transaminitis; both agents have CNS activity.

• Progression → Platinum-pemetrexed chemotherapy ± pembrolizumab

2L: Platinum-pemetrexed chemotherapy ± pembrolizumab

After MET-directed therapy. Immunotherapy has only modest single-agent activity in MET exon 14 disease, so chemotherapy-based regimens are generally preferred; weigh PD-L1 status and comorbidities.