Combination Therapy With MET Tyrosine Kinase Inhibitor and EGFR Tyrosine Kinase Inhibitor in Patients With MET-Overexpressed EGFR-Mutant Lung Adenocarcinoma
Introduction: Dysregulated MET signaling, such as MET overexpression or MET amplification (METamp), is a important mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutant lung adenocarcinoma (LUAD). Combination therapy with EGFR TKIs and MET TKIs has revealed e...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
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| Series: | JTO Clinical and Research Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364325000487 |
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| Summary: | Introduction: Dysregulated MET signaling, such as MET overexpression or MET amplification (METamp), is a important mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutant lung adenocarcinoma (LUAD). Combination therapy with EGFR TKIs and MET TKIs has revealed efficacy in these patients. This study aimed to analyze the real-world experience of TKI combination in patients with EGFR-mutant MET-overexpressed LUAD. Methods: This retrospective cohort study included patients with advanced EGFR-mutant LUAD who progressed after EGFR TKIs and were treated with combination therapy of EGFR TKIs and MET TKIs (capmatinib or tepotinib). Immunohistochemistry was used to detect MET overexpression. Results: This study included 27 patients, with a median age of 69 years; 40.7% of the patients were male individuals, and 88.9% never smoked. Overall, the treatment response of the TKI combination reported 29.6% (eight of 27) partial response, 55.6% (15 of 27) stable disease, a median progression-free survival of 7.3 months, and an overall survival of 26.9 months. The adverse events were mostly grade 1 to 2, with only one patient experiencing a grade 3 or greater event, which was peripheral edema. The most common adverse events were hypoalbuminemia (44.4%), increased creatinine (44.4%), and peripheral edema (44.4%). Eight patients underwent next-generation sequencing analysis, and two (25.0%) of them had METamp. Three patients (37.5%) had TP53 mutations, which were the most common concurrent alterations. Those with positive METamp had significantly longer median progression-free survival than those without (25.3 versus 5.8 mo; p = 0.034). Conclusions: The TKI combination reported clinical activities in patients with advanced EGFR-mutant LUAD resistant to EGFR TKIs and mild toxicity in those with MET overexpression. |
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| ISSN: | 2666-3643 |