Real-world anti-EGFR therapy in elderly mCRC patients: A monocentric analysis stratified by comorbidity and polypharmacy

Background: Elderly patients with metastatic colorectal cancer (mCRC) are increasingly encountered in clinical practice and often undertreated. While anti-EGFR monoclonal antibodies are standard in RAS wild-type disease, their feasibility in frail individuals is not fully characterized. Real-world data remain limited. Methods: We retrospectively reviewed patients aged ≥70 years with RAS/BRAF wild-type mCRC treated with anti-EGFR therapy at our center from Jan 2018 to Dec 2024. Baseline variables included age, sex, ECOG PS, comorbidities, and concomitant medications. Patients were stratified into low burden (<3 comorbidities and <5 drugs) vs. high burden (≥3 comorbidities or ≥5 drugs). Outcomes included grade ≥3 toxicities, disease control rate (DCR), and overall survival (OS). Survival was estimated using medians; predictors were explored with multivariable Cox and logistic models. Analyses were performed with R software (v4.5.1). Results: A total of 53 patients were included (median age 75.0 years; 62.3% male). ECOG PS 0–1 was observed in 52 patients. Anti-EGFR therapy was given as 1st-line in 34 patients, 2nd-line in 17, and ≥3rd-line in 2. Grade ≥3 toxicity occurred in 10 patients. Median OS was 19.5 months and DCR was 67.9%. When stratified by clinical burden, outcomes were as follows: Low burden (n=28): OS 24.0 months, DCR 64.3%, toxicity ≥G3 14.3%. High burden (n=25): OS 16.0 months, DCR 72.0%, toxicity ≥G3 24.0%. Despite similar DCR, high-burden was associated with shorter OS and higher toxicity. Multivariable analysis revealed no independent predictors of survival, though a non-significant trend toward reduced OS emerged in high-burden patients (all HRs 95% CI crossing 1) The exploratory heatmap from our cohort illustrated notable variability in OS across comorbidity and polypharmacy strata, with patterns that did not follow a linear gradient - reflecting the complexity of clinical burden. Conclusions: In this monocentric real-world analysis, anti-EGFR therapy proved a feasible and tolerable option in elderly patients with RAS/BRAF wild-type mCRC, showing manageable toxicity and encouraging disease control. Stratification by comorbidity and polypharmacy revealed meaningful variability in outcomes and offered prognostic insight beyond chronological age. Larger cohorts will be essential to validate the prognostic impact of clinical burden. These hypothesis-generating findings support the design of future inclusive trials tailored to elderly, frail, and multimorbid patients.