Liam, Chong Kin and Ahmad, Azura Rozila and Hsia, Te-Chun and Zhou, Jianying and Kim, Dong-Wan and Soo, Ross Andrew and Cheng, Ying and Lu, Shun and Shin, Sang Won and Yang, James Chih-Hsin and Zhang, Yiping and Zhao, Jun and Berghoff, Karin and Bruns, Rolf and Johne, Andreas and Wu, Yi-Long (2023) Randomized Trial of Tepotinib Plus Gefitinib versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis. Clinical Cancer Research, 29 (10). pp. 1879-1886. ISSN 1078-0432, DOI https://doi.org/10.1158/1078-0432.CCR-22-3318.
Full text not available from this repository.Abstract
Purpose: The final analyses of the INSIGHT phase II study evaluating tepotinib (a selective MET inhibitor) plus gefitinib versus chemotherapy in patients with MET-altered EGFR-mutant NSCLC (data cut-off: September 3, 2021). Patients and Methods: Adults with advanced/metastatic EGFR- mutant NSCLC, acquired resistance to first-/second-generation EGFR inhibitors, and MET gene copy number (GCN) >= 5, MET: CEP7 >= 2, or MET IHC 2+/3+ were randomized to tepotinib 500 mg (450 mg active moiety) plus gefitinib 250 mg once daily, or chemo-therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). MET-amplified subgroup analysis was preplanned. Results: Overall (N = 55), median PFS was 4.9 months versus 4.4 months stratified HR, 0.67; 90% CI, 0.35-1.28] with tepotinib plus gefitinib versus chemotherapy. In 19 patients with MET amplification (median age 60.4 years; 68.4% never-smokers; median GCN 8.8; median MET/CEP7 2.8; 89.5% with MET IHC 3+), tepotinib plus gefitinib improved PFS (HR, 0.13; 90% CI, 0.04- 0.43) and overall survival (OS; HR, 0.10; 90% CI, 0.02-0.36) versus chemotherapy. Objective response rate was 66.7% with tepotinib plus gefitinib versus 42.9% with chemotherapy; median duration of response was 19.9 months versus 2.8 months. Median duration of tepotinib plus gefitinib was 11.3 months (range, 1.1-56.5), with treatment >1 year in six (50.0%) and >4 years in three patients (25.0%). Seven patients (58.3%) had treatment-related grade >= 3 adverse events with tepotinib plus gefitinib and five (71.4%) had chemotherapy. Conclusions: Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors.
| Item Type: | Article |
|---|---|
| Funders: | healthcare business of Merck KGaA, Darmstadt, Germany |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine > Medicine Department |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 30 Sep 2025 07:58 |
| Last Modified: | 30 Sep 2025 08:31 |
| URI: | http://eprints.um.edu.my/id/eprint/50311 |
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