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Safety of Tepotinib in Patients With MET Exon 14 Skipping NSCLC and Recommendations for Management
R. Veillon, H. Sakai, X. Le, E. Felip, AB. Cortot, EF. Smit, K. Park, F. Griesinger, C. Britschgi, YL. Wu, B. Melosky, S. Baijal, GC. Jr, M. Sedova, K. Berghoff, G. Otto, PK. Paik
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Edema chemically induced drug therapy MeSH
- Exons genetics MeSH
- Hypoalbuminemia drug therapy MeSH
- Protein Kinase Inhibitors * adverse effects MeSH
- Clinical Trials, Phase II as Topic MeSH
- Creatinine therapeutic use MeSH
- Humans MeSH
- Mutation MeSH
- Lung Neoplasms * drug therapy genetics MeSH
- Nausea chemically induced MeSH
- Carcinoma, Non-Small-Cell Lung * drug therapy genetics MeSH
- Piperidines adverse effects MeSH
- Pleural Effusion MeSH
- Diarrhea MeSH
- Pyridazines adverse effects MeSH
- Pyrimidines adverse effects MeSH
- Aged MeSH
- Vomiting chemically induced MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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 Medicine Weill Cornell Medical College New York NY
Department of Oncology Vall d'Hebron Institute of Oncology Barcelona Spain
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
Medical Oncology The University of British Columbia Vancouver Canada
Netherlands Cancer Institute Amsterdam The Netherlands
Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
Thoracic Oncology Service Memorial Sloan Kettering Cancer Center New York NY
University Hospitals Birmingham NHS Foundation Trust Birmingham UK
References provided by Crossref.org
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