WCLC 2025 - Posters & ePosters-EP.12.20 A Realworld Study: Clinical Molecular Characteristics and Prognostic Factors of NSCLC With MET Alteration

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This real-world study from Xi’an Jiaotong University investigated the clinical, molecular characteristics, and prognostic factors of non-small cell lung cancer (NSCLC) patients harboring MET alterations. Among 2,180 NSCLC cases, 7.79% exhibited MET dysregulation through mutations (notably MET exon 14 skipping), amplification, or protein overexpression. The cohort included 170 MET-altered patients, predominantly elderly (median age 65), non-smokers (53%), and with adenocarcinoma histology (83%).<br /><br />Primary MET alterations (n=112) featured MET mutations (36 cases of exon 14 skipping), amplification, and overexpression. Secondary (acquired) MET alterations were observed in 58 patients. The study assessed clinicopathological features, treatments, and survival outcomes using Kaplan-Meier and Cox regression analysis. <br /><br />Key findings highlight that next-generation MET tyrosine kinase inhibitors (TKIs), particularly savolitinib, showed superior efficacy compared to crizotinib. For MET exon 14 skipping, crizotinib achieved a 60% objective response rate (ORR) versus 33.33% in MET amplification; savolitinib yielded ORRs of 53.33% in METex14 skipping and 68.75% in MET amplification cases. Median progression-free survival (mPFS) with first-line MET-TKI was 8.2 months versus 5.5 months in later-line treatment. Poor prognostic factors included TP53 co-mutations and delayed MET-TKI initiation. Median overall survival (mOS) was 24.8 months overall and 14.5 months for primary MET-altered patients. Smoking, advanced stage (IIIB-IV), and treatment modality influenced survival outcomes.<br /><br />Common adverse events from MET-TKIs included edema, liver dysfunction, diarrhea, fatigue, and nausea. The study underscores the heterogeneity of MET-altered NSCLC, the enhanced benefit of next-generation MET-TKIs, and the importance of biomarker-driven therapeutic strategies incorporating co-mutations and treatment timing to optimize patient outcomes.

Asset Subtitle

Xiao Fu

Meta Tag

Speaker Xiao Fu

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

Non-small cell lung cancer

MET alterations

MET exon 14 skipping

MET amplification

Savolitinib

Crizotinib

Next-generation MET tyrosine kinase inhibitors

Prognostic factors

TP53 co-mutations

Progression-free survival