Predictors of biomarker-directed therapy utilization in metastatic colorectal cancer: A real-world analysis.

Abstract

e15572 Background: The treatment landscape of metastatic colorectal cancer (mCRC) has evolved with identification of actionable biomarkers. However, despite inclusion of biomarker-directed therapies in NCCN guidelines, real-world uptake remains poorly defined. We evaluated predictors of receipt of biomarker-directed therapy in a large, real-world cohort of patients with BRAF V600E-mutated, KRAS G12C-mutated, and RAS/RAF wild-type (WT) mCRC. Methods: In this retrospective cohort study, we analyzed the Flatiron Health Research Database. Cohorts included patients with BRAF V600E-mutated, KRAS G12C-mutated, and RAS/RAF WT mCRC. The primary outcome was receipt of any NCCN-recommended biomarker-directed therapy at any line since FDA-approval. Univariable associations between demographic and clinical factors and therapy receipt were assessed within each cohort. Multivariable logistic regression estimated adjusted odds ratios (ORs) for treatment receipt, incorporating age, sex, baseline ECOG, primary tumor site, insurance, and stage. Results: A total of 12,226 patients were included. Among 1,336 patients with BRAF V600E, 26.2% (n = 350) received BRAF-targeted therapy. Treated patients were younger (median 66 vs 72 years, p < 0.001) and had better performance status. In multivariable analysis, increasing age (OR 0.96 per year, p < 0.001), ECOG 2 vs 0 (OR 0.60, p = 0.036), and ECOG 3 vs 0 (OR 0.19, p = 0.002) were independently associated with lower odds of therapy receipt. Race and tumor site were not associated with treatment receipt after adjustment. Among 93 patients with KRAS G12C, 10.8% (n = 10) received KRAS-targeted therapy. No significant predictors of receipt were identified, likely due to limited sample size. Among 10,797 patients with RAS/RAF WT mCRC, 44.5% (n = 4,803) received anti-EGFR targeted therapy. In multivariable analysis, older age (OR 0.98 per year, p < 0.001) and worse performance status (ECOG 2 vs 0: OR 0.79, p = 0.006; ECOG 3 vs 0: OR 0.70, p = 0.021) were associated with lower odds of treatment receipt. Male sex (OR 1.27, p < 0.001), rectal primary tumor site (OR 1.15, p = 0.008), Medicare insurance (OR 1.26, p = 0.003), and uninsured/self-pay status (OR 1.48, p < 0.001) were associated with higher odds of receiving targeted therapy, while race, ethnicity, and SES were not independent predictors. Conclusions: Receipt of guideline-recommended biomarker-directed therapy was suboptimal, particularly for BRAF V600E and KRAS G12C mutations. Older age and worse performance status consistently predicted lower treatment receipt, suggesting clinical fitness drives the gap between biomarker identification and therapy. Notably, nearly three-quarters of patients with BRAF V600E mutations did not receive targeted therapy. These findings reveal underutilization of precision oncology in mCRC and highlight the need for interventions to improve access to therapy for eligible patients.