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Long-term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the Phase II VISION study |
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| Authors: | Masahiro Morise Terufumi Kato Shingo Matsumoto Takako Inoue Tomohiro Sakamoto Takaaki Tokito Shinji Atagi Toshiyuki Kozuki Hiroaki Takeoka Kenichi Chikamori Naofumi Shinagawa Hiroshi Tanaka Eisuke Horii Svenja Adrian Rolf Bruns Andreas Johne Paul K. Paik Hiroshi Sakai |
| Affiliation: | 1. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan;2. Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan;3. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan Contribution: Investigation, Validation, Writing - review & editing;4. Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan Contribution: Investigation, Validation, Writing - review & editing;5. Department of Respiratory Medicine, Tottori University Hospital, Yonago City, Japan Contribution: Investigation, Validation, Writing - review & editing;6. Department of Internal Medicine, Kurume University School of Medicine, Kurume City, Japan Contribution: Investigation, Validation, Writing - review & editing;7. Health Management Center, JCHO Yamatokoriyama Hospital, Yamatokoriyama, Japan Contribution: Investigation, Validation, Writing - review & editing;8. Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Matsuyama City, Japan Contribution: Conceptualization, Investigation, Validation, Writing - review & editing;9. Department of Respiratory Medicine, NHO Kyushu Medical Center, Fukuoka City, Japan Contribution: Investigation, Validation, Writing - review & editing;10. Department of Oncology, NHO Yamaguchi - Ube Medical Center, Ube City, Japan Contribution: Investigation, Validation, Writing - review & editing;11. Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan Contribution: Investigation, Validation, Writing - review & editing;12. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata City, Japan Contribution: Investigation, Validation, Writing - review & editing;13. Medical Department, Merck Biopharma Co., Ltd. (an affiliate of Merck KGaA), Tokyo, Japan Contribution: Conceptualization, Methodology, Validation, Writing - review & editing;14. Global Clinical Development, Merck Healthcare KGaA, Darmstadt, Germany Contribution: Conceptualization, Data curation, Methodology, Validation, Writing - review & editing;15. Department of Biostatistics, Merck Healthcare KGaA, Darmstadt, Germany Contribution: Conceptualization, Data curation, Formal analysis, Methodology, Validation, Writing - review & editing;16. Global Clinical Development, Merck Healthcare KGaA, Darmstadt, Germany Contribution: Conceptualization, Methodology, Validation, Writing - review & editing;17. Department of Medicine, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA Contribution: Conceptualization, Investigation, Validation, Writing - review & editing;18. Department of Thoracic Oncology, Saitama Cancer Center, Kitaadachi-gun, Japan Contribution: Conceptualization, Investigation, Validation, Writing - review & editing |
| Abstract: | Tepotinib is a highly selective MET tyrosine kinase inhibitor (TKI) that has demonstrated robust and durable clinical activity in patients with MET exon 14 (METex14) skipping non–small-cell lung cancer (NSCLC). In the Phase II VISION study, patients received oral tepotinib 500 mg once daily. The primary endpoint was an objective response by an independent review committee (IRC) according to RECIST v1.1 criteria. The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Here we report the analysis of the efficacy and safety of tepotinib in all Japanese patients with advanced METex14 skipping NSCLC from VISION (n = 38) with >18 months' follow-up. The median age of the Japanese patients was 73 years (range 63–88), 39.5% of patients were ≥75 years old, 68.4% were male, 55.3% had a history of smoking, 76.3% had adenocarcinoma, and 10.5% of patients had known brain metastases at baseline. Overall, the objective response rate (ORR) was 60.5% (95% confidence interval (CI): 43.4, 76.0) with a median DOR of 18.5 months (95% CI: 8.3, not estimable). ORR in treatment-naïve patients (n = 18) was 77.8% (95% CI: 52.4, 93.6), and in patients aged ≥75 years (n = 15), ORR was 73.3% (95% CI: 44.9, 92.2). The most common treatment-related adverse event (AE) with any grade was blood creatinine increase (65.8%), which resolved following tepotinib discontinuation. Other common treatment-related AEs were peripheral edema (60.5%), hypoalbuminemia (34.2%), diarrhea (28.9%), and nausea (15.8%). In summary, tepotinib demonstrated robust and durable clinical activity irrespective of age or therapy line, with a manageable safety profile in Japanese patients with METex14 skipping NSCLC enrolled in VISION. |
| Keywords: | MET receptor tyrosine kinase METex14 skipping molecular targeting therapy non–small-cell lung cancer tepotinib |