Randomized Trial of Tepotinib Plus Gefitinib versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis
- Authors
- Liam, Chong Kin; Ahmad, Azura Rozila; Hsia, Te-Chun; Zhou, Jianying; Kim, Dong-Wan; Soo, Ross Andrew; Cheng, Ying; Lu, Shun; Shin, Sang Won; Yang, James Chih-Hsin; Zhang, Yiping; Zhao, Jun; Berghoff, Karin; Bruns, Rolf; Johne, Andreas; Wu, Yi-Long
- Issue Date
- May-2023
- Publisher
- American Association for Cancer Research
- Citation
- Clinical Cancer Research, v.29, no.10, pp 1879 - 1886
- Pages
- 8
- Indexed
- SCIE
SCOPUS
- Journal Title
- Clinical Cancer Research
- Volume
- 29
- Number
- 10
- Start Page
- 1879
- End Page
- 1886
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/63295
- DOI
- 10.1158/1078-0432.CCR-22-3318
- ISSN
- 1078-0432
1557-3265
- 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 chemotherapy. 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.
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Collections - 2. Clinical Science > Department of Medical Oncology and Hematology > 1. Journal Articles
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