Aberrant c-MET (Mesenchymal-Epithelial Transition) signaling contributes to cancer cell development, proliferation, and metastases of non-small cell lung cancer (NSCLC). MET exon 14 (METex14) skipping mutation is noted in approximately 4% of NSCLC cases and is targetable with the recently approved tyrosine kinase inhibitors capmatinib and tepotinib. Capmatinib, the focus of this review article, is a highly selective MET inhibitor approved for use in patients with METex14 mutated NSCLC. In this review, we discuss cMET as a target, the pharmacology of capmatinib, key trials of capmatinib in MET-altered lung cancer, and toxicity profile. We highlight some ongoing capmatinib clinical trials that expand their role to other subsets of patients, especially those with EGFR mutations, who develop MET alterations as a resistance pathway. We further provide our perspective on the management of METex14 NSCLC, strategies for sequencing agents, and toxicity management.
Keywords: MET exon 14 skipping mutation; Mesenchymal–Epithelial Transition gene; capmatinib; non-small cell lung cancer; tyrosine kinase inhibitor.
© 2023 Fraser et al.