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      Effective treatment of MET exon 14 skipping mutation-positive non-small cell lung cancer using capmatinib following serious maculopapular rash caused by two MET inhibitors: a case report

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          Abstract

          Background

          Multi-gene panel testing and advancements in molecular targeted therapy have improved the overall survival of patients with driver mutation-positive non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor ( MET) exon 14 skipping mutation-positive NSCLC, which remains untreated with MET inhibitors, shows a poorer prognosis than do cases of NSCLC without MET mutations. However, serious treatment-related adverse events (TRAEs) act as substantial treatment barriers.

          Case Description

          Herein, we report a case of advanced NSCLC in a male in his 40s with MET exon 14 skipping mutation. A MET-inhibitory investigational drug was administered as first-line treatment; the development of grade 3 maculopapular rash necessitated dose reduction, which resulted in disease progression. Tepotinib was then administered with dexamethasone as a third-line treatment but was discontinued owing to the re-development of the grade 3 maculopapular rash. Finally, capmatinib administration as the fifth-line treatment appeared partially effective, with no serious adverse events. The patient could successfully resume work.

          Conclusions

          This is the first report of MET exon 14 skipping mutation-positive NSCLC wherein partial response was achieved without severe TRAEs by alternating between two MET inhibitors. If no alternative treatments are available, cautious repeated re-administration of MET inhibitors after resolving serious rashes can be considered a potential approach.

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          Most cited references12

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          Capmatinib in MET Exon 14–Mutated or MET-Amplified Non–Small-Cell Lung Cancer

          Among patients with non-small-cell lung cancer (NSCLC), MET exon 14 skipping mutations occur in 3 to 4% and MET amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation.
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            Tepotinib in Non–Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations

            A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population.
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              MET Amplification and Exon 14 Splice Site Mutation Define Unique Molecular Subgroups of Non-Small Cell Lung Carcinoma with Poor Prognosis.

              Activation of MET oncogene as the result of amplification or activation mutation represents an emerging molecular target for cancer treatment. We comprehensively studied MET alterations and the clinicopathologic correlations in a large cohort of treatment-naïve non-small cell lung carcinoma (NSCLC).
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                Author and article information

                Journal
                AME Case Rep
                AME Case Rep
                ACR
                AME Case Reports
                AME Publishing Company
                2523-1995
                14 March 2024
                2024
                : 8
                : 42
                Affiliations
                [1]deptDepartment of Respiratory Medicine , Yokohama Minami Kyosai Hospital , Yokohama, Japan
                Author notes

                Contributions: (I) Conception and design: F Kashizaki; (II) Administrative support: H Koizumi, K Takahashi; (III) Provision of study materials or patients: S Okazaki; (IV) Collection and assembly of data: S Okazaki, N Tsuchiya, F Kashizaki; (V) Data analysis and interpretation: H Chen, F Kashizaki; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Fumihiro Kashizaki, MD. Department of Respiratory Medicine, Yokohama Minami Kyosai Hospital, 1-21-1, Mutsuura-higashi, Kanazawa-ku, Yokohama, Japan. Email: f.kashizaki@ 123456gmail.com .
                Author information
                https://orcid.org/0000-0003-0214-1571
                https://orcid.org/0000-0003-3074-2235
                Article
                acr-08-23-181
                10.21037/acr-23-181
                11071010
                38711889
                d8f901bd-08f2-42b3-8ecb-fcca6b5fedb3
                2024 AME Case Reports. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 25 October 2023
                : 10 February 2024
                Categories
                Case Report

                capmatinib,tepotinib,mesenchymal-epithelial transition factor (met),non-small cell lung cancer (nsclc),case report

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