Real-world survival outcomes associated with completion of adjuvant chemotherapy for stage III colon cancer

Abstract

Background: The optimal duration of adjuvant combination chemotherapy administered to patients with stage III colon cancer is debated. Our study assessed the effect of completed chemotherapy cycles on 3-year colon cancer-specific mortality, as well as the effect of dose reduction and early discontinuation of oxaliplatin in patients with 100% completion, within a real-world population. Methods: 4,147 patients undergoing major resection between 01 June 2014 and 30 April 2017 with pathological stage III colon cancer in the English National Health Service were identified. Chemotherapy data were obtained from linked administrative hospital records and a national chemotherapy dataset. Patients were stratified according to completion of < 50% ( < 6 FOLFOX cycles or < 4 CAPOX cycles), 50-92% (6-11 FOLFOX cycles or 4-7 CAPOX cycles) or 100% of cycles (12 FOLFOX cycles or 8 CAPOX cycles). Competing-risk regression analysis for 3-year colon cancer-specific death was performed with adjustment for patient, tumour and hospital-level characteristics to estimate subdistribution hazard ratios (sHR) as a measure of relative risk. Results: Patients included within our study were less fit and had increased rates of high-risk disease (T4 and/or N2 pathological staging) compared to the IDEA study. For FOLFOX, the 3-year cumulative incidence of colon cancer-specific death in patients completing 100% of cycles was 15.1% (95% CI, 12.8% to 17.6%), 18.2% (95% CI, 15.3% to 21.3%) for 50-92% of cycles and 26.4% (95% CI, 20.6% to 32.5%) for < 50% of cycles. For CAPOX, this was 12.0% (95% CI, 10.2% to 14.0%) for 100% completion of cycles, 18.2% (95% CI, 15.6% to 21.0%) for 50-92% of cycles, and 19.8% (95% CI, 15.8% to 24.1%) for < 50% cycles. Compared to 100% completion of FOLFOX cycles, colon cancer-specific death was higher in patients recorded as completing < 50% (sHR 2.17; 95% CI, 1.56 to 3.03; P = < 0.001) and 50-92% of FOLFOX cycles (sHR 1.40; 95% CI, 1.09 to 1.78; P = 0.007). Compared to 100% completion of CAPOX cycles, colon cancer-specific death was higher in patients recorded as completing < 50% (sHR 2.02; 95% CI 1.53 to 2.67; P< 0.001) and 50-92% of CAPOX cycles (sHR 1.63; 95% CI 1.27 to 2.10; P< 0.001). Dose reduction and early discontinuation of oxaliplatin did not have a statistically significant effect on mortality. Conclusions: Patients within the real world setting were more likely to have poor prognostic factors. Those who completed adjuvant chemotherapy for stage III colon cancer had improved survival rates regardless of dose reduction or early discontinuation of oxaliplatin.