Vebreltinib plus EGFR-TKI for EGFR-mutated NSCLC with MET-driven resistance: A real-world study of Chinese patients

BACKGROUND: MET amplification/overexpression is a key resistance mechanism to EGFR-tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutated non-small cell lung cancer (NSCLC). However, real-world evidence remains limited regarding the efficacy of vebreltinib plus an EGFR-TKI. METHODS: This single-center retrospective study enrolled patients with EGFR-mutant advanced NSCLC and MET amplification/overexpression after prior EGFR-TKI failure, who received vebreltinib plus an EGFR-TKI. MET alteration was confirmed by fluorescence in situ hybridization (MET gene copy number of ≥ 5 or MET/CEP7 ratio of ≥ 2.0), next-generation sequencing (MET gene copy number of ≥ 5), or immunohistochemistry (c-MET 3 + ). The efficacy was assessed by RECIST 1.1 and safety by CTCAE 5.0. RESULTS: Among the 49 patients, the combination therapy reported an objective response rate (ORR) of 46.9%, disease control rate of 91.8%, median progression-free survival (PFS) of 8.5 months [95% confidence interval (CI): 4.5-10.2], and median overall survival (OS) of 16.0 months (95% CI: 14.7-not reached). Patients with brain metastases (n = 23) reported an intracranial ORR of 69.6% and intracranial PFS of 9.7 months (95% CI: 5.12-not reached). Strong c-MET expression (immunohistochemistry 3 + ) was associated with significantly longer OS (not reached vs. 14.7 months,p = 0.033). Treatment-related adverse events occurred in 67.3% of patients (mostly grade 1-2), with peripheral edema as the most common type (30.6%). No permanent therapy discontinuation occurred. CONCLUSIONS: Vebreltinib plus an EGFR-TKI demonstrates favorable efficacy and manageable safety in real-world NSCLC patients with MET-driven resistance, with notable intracranial activity. Immunohistochemistry 3 + may serve as a practical predictive biomarker.