Background: The treatment landscape of non-small cell lung cancer (NSCLC) has transformed over the past decade, largely due to advances in therapies targeting genomic alterations. This has given patients an alternative to traditional cytotoxic chemotherapies with similar or better efficacy. C-mesenchymal-epithelial transition factor (c-Met) is a type of receptor tyrosine kinase expressed on the surfaces of various epithelial cells. Its pathway has been linked to multiple cancers, and the overexpression (OE) of c-Met is being evaluated as a therapeutic target in NSCLC.
Objectives: This study uses real-world data to characterize patients and frontline treatments according to c-Met expression level.
Methods: Patients with NSCLC seeking care at the City of Hope National Medical Center with available tumor biopsy samples were selected for manual abstraction of clinical data from electronic health records. Patients with non-squamous NSCLC, a diagnosis of metastatic disease in 2016 or later, and ≥45 days of follow-up were included. Retrospective testing on tissue samples was performed for c-Met and PD-L1, using the c-Met (SP44) OptiView formulation locked assay (FLA) and a cutoff of ≥25% 3+ staining by IHC for c-Met positivity, and standard IHC testing for PD-L1. Demographics and frontline treatments were summarized by c-Met expression level using descriptive statistics.
Results: A total of 60 eligible patients were identified, of whom 14 were c-Met OE positive (POS) (23%). Patients who were c-Met OE POS versus c-Met OE negative (NEG) were less likely to be Asian (14% vs 30%, respectively), more likely to be diagnosed with stage IV disease (57% vs 41%), and more likely to be PD-L1 POS (78% vs 41%). All other observed characteristics were similar between groups. Roughly 85% of c-Met OE POS and 91% of c-Met OE NEG patients were treated with systemic therapy during follow-up. The most common regimens in frontline among c-Met OE POS patients were platinum-based doublet (33%), immune-checkpoint inhibitor (ICI) (25%), and EGFR tyrosine kinase inhibitor (TKI) (17%) compared with EGFR TKI, ICI, ICI+Chemo, platinum-based doublet (19%) and other targeted therapies (10%) in c-Met OE NEG patients.
Conclusions: Patients with c-Met OE represent nearly a quarter of non-squamous NSCLC and exhibit high prevalence of other targetable biomarkers (PD-L1). Chemotherapy is the most common frontline therapy, signifying an unmet need for more targeted agents in this patient population.
