Real-world study of vebreltinib plus EGFR-TKI for EGFR-mutated NSCLC with MET-driven resistance

MET amplification/overexpression is a key resistance mechanism to EGFR TKIs in patients with EGFR-mutated non-small cell lung cancer (NSCLC). A retrospective study at Fujian Medical University (China) evaluated real-world outcomes with the MET inhibitor vebreltinib plus EGFR-TKI among patients with EGFR-mutant advanced NSCLC after prior EGFR-TKI failures. Among 49 patients, the combination therapy resulted in objective response rate 46.9%, disease control rate of 91.8%, median progression-free survival of 8.5 months (95% CI 4.5-10.2), and median overall survival of 16.0 months (14.7-NR). Among 23 patients with brain metastases the intracranial ORR was 69.9% and the intracranial PDS 9.7 months (95% CI 5.12-NR). Strong c-MET expression (immunohistochemistry 3+) was associated with significantly longer OS (NR versus 14.7 months; p=0.033). Treatment-related adverse events occurred in 67.3% of patients, mostly grade 1-2, and no permanent therapy discontinuations occurred. The authors conclude that vebreltinib plus an EGFR-TKI had favorable efficacy and manageable safety in real-world NSCLC patients with MET-driven resistance, with notable intracranial activity.