Prevalence, molecular characterization, and prognosis of c-Met protein overexpression in a real-world cohort of patients with non-squamous non-small cell lung cancer

Background and purpose: c-Met (also known as MET) protein is encoded by the MET proto-oncogene. In non-small cell lung cancer (NSCLC), c-Met protein overexpression (OE) drives tumorigenesis and is a therapeutic target, given recent US Food and Drug Administration approval of telisotuzumab vedotin-tllv. This retrospective analysis of tumor samples and clinical data from real-world patients with non-squamous NSCLC characterized the prevalence of c-Met protein OE, its association with messenger ribonucleic acid (mRNA) expression, MET gene amplification, programmed-death ligand 1 (PD-L1) expression, and its impact on prognosis. Patients and methods: A patient cohort was selected for manual abstraction of clinical data from electronic health records. Patients were selected based on the availability of sufficient remnant tissue for biomarker analyses, including c-Met immunohistochemistry (IHC). Comparative assessments were conducted for c-Met protein expression by IHC, MET gene amplification, mRNA expression, and PD-L1 expression levels by IHC. Results: In total, 305 and 84 patients were included in the biomarker prevalence and outcome analyses, respectively. Overall, c-Met protein OE was detected in 25% of tissue samples. Of the 212 samples with fluorescence in situ hybridization data, MET amplification was seen in 9%. Concordance of c-Met protein OE with MET mRNA levels was observed with area under the concentration-time curve values of 0.738 and 0.736 in MET OE or MET high OE, respectively, using Receiver Operating Characteristic analysis. c-Met protein OE was associated with poor prognosis (unadjusted hazard ratio for death of 2.04). Interpretation: These data suggest that c-Met protein OE is associated with MET mRNA expression, shows limited overlap with other MET aberrations, and may be linked to poor prognosis in NSCLC.