Long-term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the phase II VISION study Journal Article
| Authors: | Morise, M.; Kato, T.; Matsumoto, S.; Inoue, T.; Sakamoto, T.; Tokito, T.; Atagi, S.; Kozuki, T.; Takeoka, H.; Chikamori, K.; Shinagawa, N.; Tanaka, H.; Horii, E.; Adrian, S.; Bruns, R.; Johne, A.; Paik, P. K.; Sakai, H. |
| Article Title: | Long-term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the phase II VISION study |
| 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. © 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. |
| Keywords: | adult; controlled study; human tissue; aged; aged, 80 and over; middle aged; major clinical study; overall survival; exon; genetics; mutation; exons; clinical trial; drug tolerability; diarrhea; drug dose reduction; treatment duration; nuclear magnetic resonance imaging; follow up; edema; progression free survival; computer assisted tomography; phase 2 clinical trial; anemia; protein kinase inhibitor; nausea; carcinoma, non-small-cell lung; lung neoplasms; cohort analysis; smoking; creatinine blood level; tumor biopsy; antineoplastic activity; protein tyrosine kinase; pyrimidines; pruritus; protein kinase inhibitors; lung tumor; hypoalbuminemia; multicenter study; peripheral edema; interstitial lung disease; piperidines; stereotactic radiosurgery; disease control; pyrimidine derivative; japan; clinical laboratory; national health organization; dysgeusia; sample size; scatter factor receptor; electrocorticography; personalized medicine; non small cell lung cancer; decreased appetite; piperidine derivative; met receptor tyrosine kinase; response evaluation criteria in solid tumors; very elderly; humans; human; male; female; article; exon skipping; medical dictionary for regulatory activities; treatment interruption; japanese (people); non–small-cell lung cancer; ecog performance status; tepotinib; pyridazine derivative; pyridazines; metex14 skipping; molecular targeting therapy |
| Journal Title: | Cancer Science |
| Volume: | 115 |
| Issue: | 4 |
| ISSN: | 1347-9032 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2024-04-01 |
| Start Page: | 1296 |
| End Page: | 1305 |
| Language: | English |
| DOI: | 10.1111/cas.16107 |
| PUBMED: | 38402853 |
| PROVIDER: | scopus |
| PMCID: | PMC11006997 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
