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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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2021
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| Acceso en línea: | https://doaj.org/article/daace4b1d46746ca8c64afe95af0a459 |
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| Sumario: | 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 |
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