{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:56:41Z","timestamp":1792526201653,"version":"4.5.0"},"reference-count":10,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"\n Importance<\/jats:title>\n \n MET inhibitors have recently demonstrated clinical activity in patients with\n MET<\/jats:italic>\n exon 14 (\n MET<\/jats:italic>\n ex14)-skipping non\u2013small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with\n MET<\/jats:italic>\n ex14-skipping NSCLC in the VISION study.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with\n MET<\/jats:italic>\n ex14-skipping advanced\/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021. Cohort C (&amp;gt;18 months\u2019 follow-up) was an independent cohort, designed to confirm findings from cohort A (&amp;gt;35 months\u2019 follow-up). Data cutoff was November 20, 2022.\n <\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Patients received tepotinib, 500 mg (450 mg active moiety), once daily.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was objective response by independent review committee (RECIST v1.1). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Cohorts A and C included 313 patients (50.8% female, 33.9% Asian; median [range] age, 72 [41-94] years). The objective response rate (ORR) was 51.4% (95% CI, 45.8%-57.1%) with a median (m)DOR of 18.0 (95% CI, 12.4-46.4) months. In cohort C (n\u2009=\u2009161), an ORR of 55.9% (95% CI, 47.9%-63.7%) with an mDOR of 20.8 (95% CI, 12.6-not estimable [NE]) months was reported across treatment lines, comparable to cohort A (n\u2009=\u2009152). In treatment-naive patients (cohorts A and C; n\u2009=\u2009164), ORR was 57.3% (95% CI, 49.4%-65.0%) and mDOR was 46.4 (95% CI, 13.8-NE) months. In previously treated patients (n\u2009=\u2009149), ORR was 45.0% (95% CI, 36.8%-53.3%) and mDOR was 12.6 (95% CI, 9.5-18.5) months. Peripheral edema, the most common treatment-related adverse event, occurred in 210 patients (67.1%) (35 [11.2%] experienced grade \u22653 events).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n The findings from cohort C in this nonrandomized clinical trial supported the results from original cohort A. Overall, the long-term outcomes of VISION demonstrated robust and durable clinical activity following treatment with tepotinib, particularly in the treatment-naive setting, in the largest known clinical trial of patients with\n MET<\/jats:italic>\n ex14-skipping NSCLC, supporting the global approvals of tepotinib and enabling clinicians to implement this therapeutic approach for such patients.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT02864992<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2023.1962","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T09:30:43Z","timestamp":1685871043000},"page":"1260","source":"Crossref","is-referenced-by-count":117,"title":["Tepotinib Treatment in Patients With\n MET<\/i>\n Exon 14\u2013Skipping Non\u2013Small Cell Lung Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Julien","family":"Mazieres","sequence":"first","affiliation":[{"name":"CHU de Toulouse, Universit\u00e9 Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul K.","family":"Paik","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina C.","family":"Garassino","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"},{"name":"Now with Department of Medicine, Section of Hematology\/Oncology, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuning","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Thoracic Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Saitama Cancer Center, Kitaadachi-gun, Japan"},{"name":"Now with Department of Thoracic Oncology, Ageo Central General Hospital, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remi","family":"Veillon","sequence":"additional","affiliation":[{"name":"CHU Bordeaux, service des maladies respiratoires, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egbert F.","family":"Smit","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands"},{"name":"Now with Department of Pulmonary Diseases, Leiden University Medical Centre, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis B.","family":"Cortot","sequence":"additional","affiliation":[{"name":"Univ. 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H.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung-Ju","family":"Ahn","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Ma","sequence":"additional","affiliation":[{"name":"Medical Oncology Department of Thoracic Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"O\u2019Brate","sequence":"additional","affiliation":[{"name":"Global Medical Affairs, the healthcare business of Merck KGaA, Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Berghoff","sequence":"additional","affiliation":[{"name":"Global Patient Safety, the healthcare business of Merck KGaA, Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Bruns","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, the healthcare business of Merck KGaA, Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Otto","sequence":"additional","affiliation":[{"name":"Global Clinical Development, the healthcare business of Merck KGaA, Darmstadt, 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