Profile of Capmatinib for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC): Patient Selection and Perspectives

Abstract

Madison Fraser,1 Nagashree Seetharamu,2 Matthew Diamond,2 Chung-Shien Lee2,3 1Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, NY, USA; 2Division of Medical Oncology and Hematology, Northwell Health Cancer Institute, Lake Success, NY, USA; 3Department of Clinical Health Professions, St. John’s University, Queens, NY, USACorrespondence: Chung-Shien Lee, Email [email protected]: 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: non-small cell lung cancer, Mesenchymal–Epithelial Transition gene, MET exon 14 skipping mutation, tyrosine kinase inhibitor, capmatinib

Keywords

• non-small cell lung cancer
• mesenchymal-epithelial transition gene
• met exon 14 skipping mutation
• tyrosine kinase inhibitor
• capmatinib