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

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 t...

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Detalles Bibliográficos
Autores principales: Fraser, Madison, Seetharamu, Nagashree, Diamond, Matthew, Lee, Chung-Shien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629434/
https://www.ncbi.nlm.nih.gov/pubmed/37941971
http://dx.doi.org/10.2147/CMAR.S386799
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author Fraser, Madison
Seetharamu, Nagashree
Diamond, Matthew
Lee, Chung-Shien
author_facet Fraser, Madison
Seetharamu, Nagashree
Diamond, Matthew
Lee, Chung-Shien
author_sort Fraser, Madison
collection PubMed
description 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.
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spelling pubmed-106294342023-11-08 Profile of Capmatinib for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC): Patient Selection and Perspectives Fraser, Madison Seetharamu, Nagashree Diamond, Matthew Lee, Chung-Shien Cancer Manag Res Review 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. Dove 2023-11-03 /pmc/articles/PMC10629434/ /pubmed/37941971 http://dx.doi.org/10.2147/CMAR.S386799 Text en © 2023 Fraser et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Review
Fraser, Madison
Seetharamu, Nagashree
Diamond, Matthew
Lee, Chung-Shien
Profile of Capmatinib for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC): Patient Selection and Perspectives
title Profile of Capmatinib for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC): Patient Selection and Perspectives
title_full Profile of Capmatinib for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC): Patient Selection and Perspectives
title_fullStr Profile of Capmatinib for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC): Patient Selection and Perspectives
title_full_unstemmed Profile of Capmatinib for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC): Patient Selection and Perspectives
title_short Profile of Capmatinib for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC): Patient Selection and Perspectives
title_sort profile of capmatinib for the treatment of metastatic non-small cell lung cancer (nsclc): patient selection and perspectives
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629434/
https://www.ncbi.nlm.nih.gov/pubmed/37941971
http://dx.doi.org/10.2147/CMAR.S386799
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