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

Area of Science:

• Oncology
• Medical Genetics
• Pharmacology

Background:

• MET amplification/overexpression is a significant resistance mechanism to EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC).
• Limited real-world data exists on the efficacy of vebreltinib in combination with an EGFR-TKI for this patient population.

Purpose of the Study:

• To evaluate the real-world efficacy and safety of vebreltinib plus an EGFR-TKI in patients with EGFR-mutant advanced NSCLC and MET amplification/overexpression.
• To assess the treatment outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
• To investigate the intracranial activity and the role of c-MET expression as a predictive biomarker.

Main Methods:

• A single-center retrospective study involving 49 patients with EGFR-mutant advanced NSCLC and MET alteration post-EGFR-TKI failure.
• MET alteration was confirmed using fluorescence in situ hybridization, next-generation sequencing, or immunohistochemistry (c-MET 3+).
• Efficacy was assessed using RECIST 1.1 criteria, and safety was evaluated per CTCAE 5.0.

Main Results:

• The combination therapy achieved an ORR of 46.9%, a disease control rate of 91.8%, median PFS of 8.5 months, and median OS of 16.0 months.
• In patients with brain metastases (n=23), intracranial ORR was 69.6% with an intracranial PFS of 9.7 months.
• Strong c-MET expression (IHC 3+) correlated with significantly longer OS (not reached vs. 14.7 months, p=0.033). Adverse events were mostly grade 1-2, with peripheral edema being most common.

Conclusions:

• Vebreltinib plus an EGFR-TKI demonstrates favorable real-world efficacy and manageable safety in NSCLC patients with MET-driven resistance.
• The combination therapy exhibits notable intracranial activity, beneficial for patients with brain metastases.
• Immunohistochemistry 3+ c-MET expression may serve as a practical predictive biomarker for treatment response.