De-escalation in the elderly: Adjuvant fluoropyrimidine monotherapy vs oxaliplatin-based regimens in stage 3 colon cancer patients aged ≥ 75.

Abstract

e15646 Background: Addition of oxaliplatin to adjuvant fluoropyrimidine therapy (FOLFOX/CAPOX) is the established standard of care for stage III colon cancer but its benefit in patients ≥75 years remains controversial, as pivotal trials (MOSAIC, NSABP C-07) largely underrepresented this demographic. Pooled analyses (ACCENT database) suggest that survival benefits of oxaliplatin diminish and toxicity increase with age. We aimed to evaluate the therapeutic value and safety burden of adding oxaliplatin to adjuvant therapy in elderly patients. Methods: Using TriNetX global network, we identified patients ≥75 years with resected stage III colon cancer who initiated adjuvant chemotherapy within 4 months of colectomy. Two cohorts were defined: Monotherapy (fluorouracil/capecitabine; n = 262) and Combination Therapy (fluorouracil/capecitabine plus oxaliplatin; n = 427). 1:1 propensity score matching (PSM) was performed for demographics, comorbidities (CKD, HTN, DM, COPD, HF, IHD), markers of geriatric frailty (wheelchair/oxygen use, age-related debility, cachexia, reduced mobility, and need for assistance), disease severity (intestinal obstruction at diagnosis) and baseline neuropathy. Outcomes were 5 year Overall Survival (OS), 5-year incidence of metastases; 180 day health care utilization (HCU) and drug induced polyneuropathy rates and 90-day neutropenia and thrombocytopenia (grade 2); calculated from first chemotherapy. Results: Before matching, combination cohort was significantly younger with fewer comorbidities and baseline neuropathy. After matching (n = 195/arm), 5 year OS was numerically higher in the combination therapy cohort but did not reach statistical significance compared to monotherapy (74.3% vs 61.9%; p = 0.08). Addition of oxaliplatin was associated with higher 180 day health care utilization (42.1% vs 31.8%; HR 0.756, 95% CI 0.58–0.98; p = 0.036), reflecting increased toxicity without significant survival gain. Conclusions: In patients ≥75 with stage III colon cancer, addition of oxaliplatin to adjuvant therapy increases the burden of health care utilization without adding a statistically significant survival benefit. These real world findings align with ACCENT pooled analyses and support treatment de-escalation as fluoropyrimidine monotherapy preserves efficacy while minimizing toxicity. Priority should be given to quality of life and geriatric assessment when selecting adjuvant regimens for the oldest old. Outcome Monotherapy cohort (n= 195) Combination therapy cohort (n= 195) Hazard Ratio/ Risk Ratio (95% CI) P-value 5 year Survival Probability 61.91% 74.53% - 0.08 5 year Metastasis 20.21% 21.88% 0.92 (0.66, 1.36) 0.69 HCU 31.8% 42.1% 0.76 (0.58, 0.98) 0.036 Neutropenia 9.23% 23.08% 0.4 (0.24,0.67) <0.001 Thrombocytopenia 9.23% 33.33% 0.277 (0.17,0.45) <0.001 Polyneuropathy 8.8% 23.9% 0.37 (0.22,0.63) <0.001