Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics

Matthew Z Guo,1 Kristen A Marrone,1 Alexander Spira,1– 3 David M Waterhouse,3,4 Susan C Scott1 1Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; 2Virginia Cancer Specialists Research Institute, Fairfax, VA, USA; 3US Oncology, The Woodlands,...

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Autores principales:	Guo MZ, Marrone KA, Spira A, Waterhouse DM, Scott SC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	capmatinib met exon 14 skipping non-small cell lung cancer foundationone cdx Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/daace4b1d46746ca8c64afe95af0a459
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spelling	oai:doaj.org-article:daace4b1d46746ca8c64afe95af0a4592021-11-23T18:43:00ZTargeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics1178-6930https://doaj.org/article/daace4b1d46746ca8c64afe95af0a4592021-11-01T00:00:00Zhttps://www.dovepress.com/targeted-treatment-of-non-small-cell-lung-cancer-focus-on-capmatinib-w-peer-reviewed-fulltext-article-OTThttps://doaj.org/toc/1178-6930Matthew Z Guo,1 Kristen A Marrone,1 Alexander Spira,1– 3 David M Waterhouse,3,4 Susan C Scott1 1Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; 2Virginia Cancer Specialists Research Institute, Fairfax, VA, USA; 3US Oncology, The Woodlands, TX, USA; 4Oncology Hematology Care, Cincinnati, OH, UsaCorrespondence: Susan C ScottJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, 201 N Broadway, Baltimore, MD, 21287, USATel +1410-955-8893Fax +1410-367-2194Email sscott89@jhmi.eduAbstract: MET dysregulation promoting tumorigenesis in non-small cell lung cancer (NSCLC) is associated with worse outcomes following chemotherapy as compared to non-driver mutated NSCLC and occurs either through mutations causing MET exon 14 skipping (METex14) or gene amplification and overexpression that result in enhanced receptor signaling. Capmatinib is the first FDA-approved targeted therapy for NSCLC with METex14 skipping mutations, approved in 2020. FoundationOne® CDx, a comprehensive genomic profiling test for solid tumors, was concurrently approved as a companion diagnostic for capmatinib use. The GEOMETRY mono-1 phase II trial of capmatinib monotherapy demonstrated an overall response rate (ORR) of 68% in treatment naïve (n=28) and 41% in pre-treated (n=69) METex14 skipping advanced NSCLC; in MET amplified advanced NSCLC (gene copy number ≥ 10) ORRs of 40% in treatment naïve and 29% in pre-treated disease was seen. This review outlines the clinical data supporting capmatinib approval in the treatment of NSCLC and FoundationOne® CDx approval as a companion diagnostic. We detail the practical clinical administration of capmatinib, including dosing and toxicity management, compare capmatinib to other approved and investigational MET-targeted therapies, discuss limitations of capmatinib, and highlight ongoing trials of capmatinib in combinatorial approaches.Keywords: capmatinib, MET exon 14 skipping, non-small cell lung cancer, FoundationOne CDxGuo MZMarrone KASpira AWaterhouse DMScott SCDove Medical Pressarticlecapmatinibmet exon 14 skippingnon-small cell lung cancerfoundationone cdxNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncoTargets and Therapy, Vol Volume 14, Pp 5321-5331 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	capmatinib met exon 14 skipping non-small cell lung cancer foundationone cdx Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	capmatinib met exon 14 skipping non-small cell lung cancer foundationone cdx Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Guo MZ Marrone KA Spira A Waterhouse DM Scott SC Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics
description	Matthew Z Guo,1 Kristen A Marrone,1 Alexander Spira,1– 3 David M Waterhouse,3,4 Susan C Scott1 1Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; 2Virginia Cancer Specialists Research Institute, Fairfax, VA, USA; 3US Oncology, The Woodlands, TX, USA; 4Oncology Hematology Care, Cincinnati, OH, UsaCorrespondence: Susan C ScottJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, 201 N Broadway, Baltimore, MD, 21287, USATel +1410-955-8893Fax +1410-367-2194Email sscott89@jhmi.eduAbstract: MET dysregulation promoting tumorigenesis in non-small cell lung cancer (NSCLC) is associated with worse outcomes following chemotherapy as compared to non-driver mutated NSCLC and occurs either through mutations causing MET exon 14 skipping (METex14) or gene amplification and overexpression that result in enhanced receptor signaling. Capmatinib is the first FDA-approved targeted therapy for NSCLC with METex14 skipping mutations, approved in 2020. FoundationOne® CDx, a comprehensive genomic profiling test for solid tumors, was concurrently approved as a companion diagnostic for capmatinib use. The GEOMETRY mono-1 phase II trial of capmatinib monotherapy demonstrated an overall response rate (ORR) of 68% in treatment naïve (n=28) and 41% in pre-treated (n=69) METex14 skipping advanced NSCLC; in MET amplified advanced NSCLC (gene copy number ≥ 10) ORRs of 40% in treatment naïve and 29% in pre-treated disease was seen. This review outlines the clinical data supporting capmatinib approval in the treatment of NSCLC and FoundationOne® CDx approval as a companion diagnostic. We detail the practical clinical administration of capmatinib, including dosing and toxicity management, compare capmatinib to other approved and investigational MET-targeted therapies, discuss limitations of capmatinib, and highlight ongoing trials of capmatinib in combinatorial approaches.Keywords: capmatinib, MET exon 14 skipping, non-small cell lung cancer, FoundationOne CDx
format	article
author	Guo MZ Marrone KA Spira A Waterhouse DM Scott SC
author_facet	Guo MZ Marrone KA Spira A Waterhouse DM Scott SC
author_sort	Guo MZ
title	Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics
title_short	Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics
title_full	Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics
title_fullStr	Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics
title_full_unstemmed	Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics
title_sort	targeted treatment of non-small cell lung cancer: focus on capmatinib with companion diagnostics
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/daace4b1d46746ca8c64afe95af0a459
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Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics

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