INTRODUCTION: The MET inhibitor tepotinib demonstrated durable clinical activity in patients with advanced MET exon 14 (METex14) skipping NSCLC. We report detailed analyses of adverse events of clinical interest (AECIs) in VISION, including edema, a class effect of MET inhibitors. PATIENTS AND METHODS: Incidence, management, and time to first onset/resolution were analyzed for all-cause AECIs, according to composite categories (edema, hypoalbuminemia, creatinine increase, and ALT/AST increase) or individual preferred terms (pleural effusion, nausea, diarrhea, and vomiting), for patients with METex14 skipping NSCLC in the phase II VISION trial. RESULTS: Of 255 patients analyzed (median age: 72 years), edema, the most common AECI, was reported in 69.8% (grade 3, 9.4%; grade 4, 0%). Median time to first edema onset was 7.9 weeks (range: 0.1-58.3). Edema was manageable with supportive measures, dose reduction (18.8%), and/or treatment interruption (23.1%), and rarely prompted discontinuation (4.3%). Other AECIs were also manageable and predominantly mild/moderate: hypoalbuminemia, 23.9% (grade 3, 5.5%); pleural effusion, 13.3% (grade ≥ 3, 5.1%); creatinine increase, 25.9% (grade 3, 0.4%); nausea, 26.7% (grade 3, 0.8%), diarrhea, 26.3% (grade 3, 0.4%), vomiting 12.9% (grade 3, 1.2%), and ALT/AST increase, 12.2% (grade ≥ 3, 3.1%). GI AEs typically occurred early and resolved in the first weeks. CONCLUSION: Tepotinib was well tolerated in the largest trial of a MET inhibitor in METex14 skipping NSCLC. The most frequent AEs were largely mild/moderate and manageable with supportive measures and/or dose reduction/interruption, and caused few withdrawals in this elderly population.

CHU Bordeaux Service des Maladies Respiratoires Bordeaux France

Cytel Czech Republic s r o Prague Czech Republic

Department of Clinical Oncology Hospital Sírio Libanês São Paulo Brazil

Department of Medical Oncology and Hematology Comprehensive Cancer Center Zurich University Hospital Zurich Zurich Switzerland

Department of Oncology Vall d'Hebron Institute of Oncology Barcelona Spain

Department of Thoracic Head and Neck Medical Oncology The University of Texas MD Anderson Cancer Center Houston TX

Department of Thoracic Oncology Saitama Cancer Center Saitama Japan

Global Clinical Development the healthcare business of Merck KGaA Darmstadt Germany

Global Patient Safety the healthcare business of Merck KGaA Darmstadt Germany

Guangdong Lung Cancer Institute Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences Guangzhou China

Medical Oncology The University of British Columbia Vancouver Canada

Netherlands Cancer Institute Amsterdam The Netherlands

Pius Hospital University Medicine Oldenburg Department of Hematology and Oncology University Department Internal Medicine Oncology Oldenburg Germany

Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea

Thoracic Oncology Service Memorial Sloan Kettering Cancer Center New York NY; Department of Medicine Weill Cornell Medical College New York NY

Univ Lille CHU Lille CNRS Inserm Institut Pasteur de Lille UMR9020 UMR S 1277 Canther F 59000 Lille France

University Hospitals Birmingham NHS Foundation Trust Birmingham UK

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