# Combination Therapy With MET Tyrosine Kinase Inhibitor and EGFR Tyrosine Kinase Inhibitor in Patients With MET-Overexpressed EGFR-Mutant Lung Adenocarcinoma

## TL;DR

Combining MET and EGFR inhibitors helps treat lung cancer patients resistant to EGFR drugs, with manageable side effects.

## Contribution

Reports real-world efficacy and safety of MET-EGFR combination therapy in MET-overexpressed EGFR-mutant lung cancer.

## Key findings

- Combination therapy achieved 29.6% partial response and 55.6% stable disease in resistant patients.
- Median progression-free survival was 7.3 months, with overall survival of 26.9 months.
- Patients with MET amplification had significantly longer progression-free survival (25.3 vs. 5.8 months).

## Abstract

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.

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.

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).

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.