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Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations

 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  ;  Xiuning Le 
 NEW ENGLAND JOURNAL OF MEDICINE, Vol.383(10) : 931-943, 2020-09 
Journal Title
Issue Date
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents / adverse effects ; Antineoplastic Agents / therapeutic use ; Carcinoma, Non-Small-Cell Lung / drug therapy* ; Carcinoma, Non-Small-Cell Lung / genetics ; Edema / chemically induced ; Exons ; Female ; Humans ; Lung Neoplasms / drug therapy* ; Lung Neoplasms / genetics ; Male ; Middle Aged ; Mutation* ; Piperidines / adverse effects ; Piperidines / therapeutic use* ; Protein Kinase Inhibitors / adverse effects ; Protein Kinase Inhibitors / therapeutic use* ; Proto-Oncogene Proteins c-met / antagonists & inhibitors* ; Proto-Oncogene Proteins c-met / genetics ; Pyridazines / adverse effects ; Pyridazines / therapeutic use* ; Pyrimidines / adverse effects ; Pyrimidines / therapeutic use*
Background: 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. Methods: In 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. Results: As 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. Conclusions: Among 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.).
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
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