• Paul K Paik, Enriqueta Felip, Remi Veillon, Hiroshi Sakai, Alexis B Cortot, Marina C Garassino, Julien Mazieres, Santiago Viteri, Helene Senellart, Jan Van Meerbeeck, Jo Raskin, Niels Reinmuth, Pierfranco Conte, Dariusz Kowalski, Byoung Chul Cho, Jyoti D Patel, Leora Horn, Frank Griesinger, Ji-Youn Han, Young-Chul Kim, Gee-Chen Chang, Chen-Liang Tsai, James C-H Yang, Yuh-Min Chen, Egbert F Smit, Anthonie J van der Wekken, Terufumi Kato, Dilafruz Juraeva, Christopher Stroh, Rolf Bruns, Josef Straub, Andreas Johne, Jürgen Scheele, John V Heymach, and Xiuning Le.
• From Memorial Sloan Kettering Cancer Center, New York (P.K.P.); the Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (E.F.), and Dr. Rosell Oncology Institute, Dexeus University Hospital, Quirónsalud Group (S.V.), Barcelona; Centre Hospitaliere Universitaire (CHU) Bordeaux, Service des Maladies Respiratoires, Bordeaux (R.V.), Université de Lille, CHU Lille, Thoracic Oncology Department, Centre National de la Recherche Scientifique, INSERM, Institut Pasteur de Lille, UMR9020-UMR-S 1277-Canther, Lille (A.B.C.), CHU de Toulouse, Institut Universitaire du Cancer de Toulouse, Université Paul Sabatier, Toulouse (J.M.), and Institut de Cancérologie de l'Ouest Rene Gauducheau Centre, Saint-Herblain (H. Senellart) - all in France; Saitama Cancer Center, Saitama (H. Sakai), and the Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama (T.K.) - both in Japan; the Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (M.C.G.), and the Department of Surgery, Oncology and Gastroenterology, University of Padua and Oncologia Medica 2, Istituto Oncologico Veneto, IRCCS, Padua (P.C.) - both in Italy; Antwerp University Hospital, Edegem, Belgium (J.V.M., J.R.); Asklepios Lung Clinic, Munich-Gauting (N.R.), Pius Hospital Oldenburg, University Medicine Oldenburg, Oldenburg (F.G.), Translational Medicine, Department of Bioinformatics (D.J.), Translational Innovation Platform, Oncology (C.S.), the Department of Biostatistics (R.B.), Translational Medicine, Department of Clinical Biomarkers and Companion Diagnostics (J. Straub), and Global Clinical Development (A.J., J. Scheele), Merck, Darmstadt - all in Germany; the Department of Lung Cancer and Thoracic Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (D.K.); Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), the Center for Lung Cancer, National Cancer Center, Goyang (J.-Y.H.), and Chonnam National University Medical School and Hwasun Hospital, Hwasun (Y.-C.K.) - all in South Korea; Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago (J.D.P.); the Department of Medicine, Vanderbilt Ingram Cancer Center, Nashville (L.H.); the Faculty of Medicine, School of Medicine, National Yang-Ming University (G.-C.C.), the Division of Chest Medicine, Department of Internal Medicine, Tri-service General Hospital, National Defense Medical Center (C.-L.T.), National Taiwan University Hospital (J.C.-H.Y.), and the Department of Chest Medicine, Taipei Veterans General Hospital, and School of Medicine, National Yang-Ming University (Y.-M.C.), Taipei, and the Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung (G.-C.C.) - both in Taiwan; the Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (E.F.S.), and the Department of Pulmonology, University of Groningen and University Medical Center Groningen, Groningen (A.J.W.) - both in the Netherlands; and M.D. Anderson Cancer Center, University of Texas, Houston (J.V.H., X.L.).
• N. Engl. J. Med. 2020 Sep 3; 383 (10): 931-943.

BackgroundA 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.MethodsIn this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation. The primary end point was the objective response by independent review among patients who had undergone at least 9 months of follow-up. The response was also analyzed according to whether the presence of a MET exon 14 skipping mutation was detected on liquid biopsy or tissue biopsy.ResultsAs of January 1, 2020, a total of 152 patients had received tepotinib, and 99 patients had been followed for at least 9 months. The response rate by independent review was 46% (95% confidence interval [CI], 36 to 57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was similar regardless of the previous therapy received for advanced or metastatic disease. Adverse events of grade 3 or higher that were considered by investigators to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Adverse events led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment.ConclusionsAmong patients with advanced NSCLC with a confirmed MET exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients. Peripheral edema was the main toxic effect of grade 3 or higher. (Funded by Merck [Darmstadt, Germany]; VISION ClinicalTrials.gov number, NCT02864992.).Copyright © 2020 Massachusetts Medical Society.

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