The landscape of MET alterations in non-small cell lung cancer in Southeast China: A real-world study.

Abstract

e20686 Background: MET alterations are critical oncogenic drivers in NSCLC. However, real-world data regarding the distribution, clinical characteristics, treatment and outcomes remain limited. Methods: We retrospectively analyzed 574 MET-altered NSCLC patients treated at a comprehensive hospital in southeastern China(July 2021-December 2023). MET alterations were categorized into MET Overexpression, MET Amplification, MET Exon14 Skipping, and MET Other Mutation, identified via PCR, IHC, NGS or FISH. MET-OE-high was defined as IHC 2+/3+. Baseline, pathological, co-mutation, treatment, and survival data were collected. With a minimum follow-up of 2 years, we analyzed 24-month survival and evaluated the prognostic impact of MET-TKIs. Results: Of 574 patients: MET-OE(81.4%), MET-amp(11.0%), MET-ex14(4.70%), and Others(2.96%). Subgroups were predominantly middle-aged/elderly males, > 40% had smoking history and > 35% hypertension. Specimens were mainly from bronchoscopic or percutaneous biopsies. Pathologically, adenocarcinoma predominated across subtypes; in MET-OE, its prevalence increased with IHC intensity (p < 0.05). MET-amp exhibited the highest rates of advanced stage (87.3%), bone metastases (36.5%), and brain metastases (17.5%). TP53 was the top co-mutation(20.7%–25.0%). Targeted therapy predominated (First-line 54.6%, Second-line 38.9%), followed by chemo-immunotherapy, whereas specific MET-TKI utilization was only 10.5%. 24-month overall survival was lower in MET-amp (44.4%) and MET-ex14(48.1%) compared to MET-OE(57.2%) and Others(58.8%). MET-TKIs showed survival benefit trends in MET-OE-high, MET-ex14 and MET-amp. Post-PSM 24-month OS (treated vs untreated): 69.2% vs. 38.5% (MET-OE-high), 71.4% vs. 25.0% (MET-ex14) and 47.4% vs. 42.9% (MET-amp). Conclusions: Despite demographic similarities, MET subtypes exhibit significant pathological, co-mutational, therapeutic and prognostic heterogeneity. MET-TKIs show potential benefits for MET-OE and MET-ex14, warranting large-scale validation.