BMC cancer · 2026
The landscape of MET alterations in non-small cell lung cancer in Southeastern China: a real-world study.
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Zheng Sisi, Zuo Ziyi, Lin Rixu, Zhang Xiaoxiao, Huang Lujie, Cai Mengsi, Ye Yifan, Yao Dan, Huang Xiaoying
Аннотация
BACKGROUND: MET is a key driver in NSCLC yet comprehensive, multi-subtype real-world data in China are lacking.
METHODS: Real-world data were collected from MET-altered NSCLC patients diagnosed at a comprehensive hospital in southeastern China (July 2021-December 2023). Four subgroups were analyzed: MET IHC-Positive, MET Amplification, MET Exon 14 skipping, and MET Other Mutations. Demographics, risk factors, comorbidities, pathology, co-mutation, and treatment patterns were compared. With 2-year follow-up, survival outcomes and MET-TKI benefit were analyzed.
RESULTS: Among 574 patients: MET IHC-Pos (81.4%), MET-Amp (11.0%), MET-Ex14 (4.70%), and Others (2.96%). Patients were predominantly elderly, male, with > 40% smoking history and > 35% hypertension. Pathological specimens were mainly obtained via bronchoscopy or percutaneous lung puncture. Adenocarcinoma dominated all subtypes (> 70%), increasing with IHC intensity in MET IHC-Pos (p < 0.05). MET-Amp showed the highest advanced stage (87.3%), bone (36.5%) and brain metastasis (17.5%). TP53 was the most common co-mutation (20.7%-25.0%). Targeted therapy predominated (Line 1st: 54.6%, Line 2nd: 38.9%), followed by chemotherapy plus immunotherapy. The 24-month OS was lower in MET-Amp (44.4%) and MET-Ex14 (48.1%) than in MET IHC-Pos (57.2%) and Others (58.8%). The 24-month OS (MET-TKI treated vs. untreated) was: 69.2% vs. 38.5% (MET IHC-Pos 2 + /3 +), 71.4% vs. 25.0% (MET-Ex14), and 47.4% vs. 42.9% (MET-Amp).
CONCLUSIONS: MET alterations occur predominantly in the elderly, males, and smokers. MET-Ex14 shows driver-dependent characteristics with clear MET-TKI benefit. MET-Amp presents the most aggressive phenotype. MET IHC-Pos predominates (> 80%) with heterogeneity; the 2 + /3 + may benefit from MET-TKI. These findings inform subtype-based management of MET-altered NSCLC in southeastern China.
METHODS: Real-world data were collected from MET-altered NSCLC patients diagnosed at a comprehensive hospital in southeastern China (July 2021-December 2023). Four subgroups were analyzed: MET IHC-Positive, MET Amplification, MET Exon 14 skipping, and MET Other Mutations. Demographics, risk factors, comorbidities, pathology, co-mutation, and treatment patterns were compared. With 2-year follow-up, survival outcomes and MET-TKI benefit were analyzed.
RESULTS: Among 574 patients: MET IHC-Pos (81.4%), MET-Amp (11.0%), MET-Ex14 (4.70%), and Others (2.96%). Patients were predominantly elderly, male, with > 40% smoking history and > 35% hypertension. Pathological specimens were mainly obtained via bronchoscopy or percutaneous lung puncture. Adenocarcinoma dominated all subtypes (> 70%), increasing with IHC intensity in MET IHC-Pos (p < 0.05). MET-Amp showed the highest advanced stage (87.3%), bone (36.5%) and brain metastasis (17.5%). TP53 was the most common co-mutation (20.7%-25.0%). Targeted therapy predominated (Line 1st: 54.6%, Line 2nd: 38.9%), followed by chemotherapy plus immunotherapy. The 24-month OS was lower in MET-Amp (44.4%) and MET-Ex14 (48.1%) than in MET IHC-Pos (57.2%) and Others (58.8%). The 24-month OS (MET-TKI treated vs. untreated) was: 69.2% vs. 38.5% (MET IHC-Pos 2 + /3 +), 71.4% vs. 25.0% (MET-Ex14), and 47.4% vs. 42.9% (MET-Amp).
CONCLUSIONS: MET alterations occur predominantly in the elderly, males, and smokers. MET-Ex14 shows driver-dependent characteristics with clear MET-TKI benefit. MET-Amp presents the most aggressive phenotype. MET IHC-Pos predominates (> 80%) with heterogeneity; the 2 + /3 + may benefit from MET-TKI. These findings inform subtype-based management of MET-altered NSCLC in southeastern China.