6D-03 - Epidemiology of MET gene mRNA expression in metastatic colorectal cancer: analyses of a real-world clinicogenomic database

Background: The MET proto-oncogene encodes the c-Met protein and is associated with promotion of tumor growth, angiogenesis, metastasis, and drug resistance.

Objectives: Our objective was to describe the prevalence of increased MET mRNA expression corresponding to c-Met protein expression and its associations with demographic and clinical characteristics among patients with metastatic colorectal cancer (mCRC) in a US-based clinicogenomic database.

Methods: We conducted a retrospective cohort study of patients diagnosed with mCRC between 2014 and 2023 using the ConcertAI Patient360™ electronic health record database with linkage to Caris Life Sciences genomic data. Patients were followed from first-line therapy (index time) until death or end of study follow up (Jan 2024). A 5-fold cross-validated and cross-cohort tested machine learning classifier trained on c-Met protein immunohistochemistry (IHC) labels (defined as 3+, ≥10% staining) was applied to derive prevalence of increased MET gene mRNA expression from whole transcriptome sequencing. Prevalence rate differences and rate ratios (RR) with robust 95% confidence intervals (CI) were calculated using modified Poisson regression.

Results: From an overall cohort of 1,020 patients with mCRC with a median age of 63 at metastatic diagnosis, 46% were female and 70% were non-Hispanic White, 20% non-Hispanic Black, 1% non-Hispanic Asian, and 5% Hispanic. At mCRC diagnosis, 81% had an ECOG performance status of 0-1 and 71% were diagnosed with de novo metastatic disease. The overall prevalence of increased MET gene mRNA expression corresponding to 3+, ≥10% c-Met IHC staining in the cohort was 35% (95% CI 32-38) and most samples (84%) were collected prior to treatment initiation. Patients with and without increased expression at this cutoff were broadly similar with respect to demographic and clinical characteristics. However, trends suggested greater prevalence of increased expression among individuals that were ages ≥75 years (42%), non-Hispanic Black (40%), had body mass index (BMI) <18.5 kg/m2 (53%), and ECOG of ≥2 (44%); and lower prevalence with rectum as primary tumor site (29%) and microsatellite instability-high (28%). BMI <18.5 kg/m2 (vs 18.5-24.9, RR 1.47, 95% CI 1.03-2.10), ECOG of ≥2 (vs 0-1, RR 1.29, 95% CI 1.00-1.68) and colon (vs rectum, RR 1.29, 95% CI 1.03-1.62) were significantly associated with increased mRNA expression.

Conclusions: Increased MET gene mRNA expression was observed among 35% of patients with mCRC in our cohort and was positively correlated with older age, low BMI at metastatic diagnosis, non-Hispanic Black race/ethnicity, poor performance status, colon (vs rectum) as primary site, and microsatellite stable (vs MSI-H) tumors.