Biomarker matched biologic use in patients with metastatic colorectal cancer (mCRC).

Abstract

40 Background: The use of biologic therapy for patients with mCRC is incompletely characterized. We evaluated receipt of biomarker matched guideline concordant treatment with VEGF inhibitors (VEGFi), EGFR antibodies (EGFRa), and immune checkpoint inhibitors (ICI), assessing treatment by sociodemographic, clinical, and practice-level factors. Methods: Using an electronic health record-derived dataset from the Flatiron Health Research Database, we evaluated patients who were diagnosed with mCRC from 2016–2024; had documented RAS, BRAF, and MMR/MSI testing (from –12 to +6 months from diagnosis); and received systemic therapy (from diagnosis to the later of +3 months from diagnosis or last test result date). We determined patients’ guideline concordant treatment options based on biomarker results and tumor sidedness, according to contemporaneous clinical guidelines and drug approvals. Our outcome was whether a patient received appropriate biomarker-matched treatment. We used multivariable logistic regression to determine the association between patient factors and receipt of matched treatment with VEGFi, EGFRa, and ICI. Results: Of 11,009 eligible patients (median age 63 years, 43.8% female, 59.0% non-Hispanic White), a majority of patients (57.4%) were only eligible for VEGFi. Most patients (69.1%) received matched therapy, though receipt was lower in the VEGFi-only group (65.8%) compared to those eligible for EGFRa or VEGFi (73.2%) or any ICI (75.6%; group p-value < .001). In multivariable analysis, we did not observe differences in biomarker-matched treatment by age, sex, race/ethnicity, insurance type, area-level socioeconomic status, initial stage, or tumor sidedness. Matched biologic treatment was lower in patients with worse performance status (PS; PS 3–4 vs 0, aOR 0.59, 95% CI 0.43–0.80). Treatment was also lower in patients with biomarker results associated with VEGFi-only eligibility, including RAS mutations (aOR 0.85 vs wildtype, 95% CI 0.78–0.93), BRAF mutations (aOR 0.84 vs wildtype, 95% CI 0.73–0.98). Deficient MMR/high MSI was associated with higher odds of matched treatment (aOR 1.25 vs proficient MMR/MSS, 95% CI 1.03–1.52). Subgroup analysis showed that each of these associations were most pronounced in VEGFi-only patients. Conclusions: In this cohort study, nearly one third of mCRC patients did not receive biomarker-guided biologic treatment. Differences in treatment receipt were driven by patients only eligible for VEGFi, in whom poor PS may be a surrogate for VEGFi contraindications. Notably, we did not find differences in treatment by patient sociodemographic factors. Biologic receipt by treatment eligibility group. Treatment Eligibility % Matched Biologic % Unmatched Biologic % No Biologic VEGFi only( n =6318, 57.4%) 65.8 4.3 29.9 EGFRa or VEGFi( n =4195, 38.1%) 73.2 0.6 26.2 ICI +/- others( n =496, 4.5%) 75.6 10.3 14.1 TOTAL ( N =11009) 69.1 3.1 27.8