Comparative Effectiveness of Oral Fluoropyrimidines Versus FOLFOX as Adjuvant Therapy for Stage III Colon Cancer: A...

Oxaliplatin-based chemotherapy is the standard adjuvant treatment for stage III colon cancer, but oral fluoropyrimidines remain widely used for patients unsuitable for combination therapy. Real-world data comparing these strategies are limited.

We conducted a retrospective cohort study of patients with stage III colon cancer who received adjuvant chemotherapy at Kaohsiung Veterans General Hospital (2017-2021). Using a 12-month landmark design, we compared disease-free survival (DFS) between patients receiving FOLFOX (IV-Only) versus oral fluoropyrimidines (PO-Only). The primary analysis used overlap-weighted restricted mean survival time (RMST) differences to quantify absolute treatment effects. Cox proportional hazards regression provided complementary hazard ratio estimates.

Of 157 patients included, 58 (36.9%) received FOLFOX and 99 (63.1%) received oral fluoropyrimidines. During median follow-up of 36 months, 22 DFS events occurred. The 3-year DFS was 93.1% versus 76.5% for IV-Only and PO-Only groups, respectively. The primary analysis showed that patients receiving FOLFOX had 4.0 additional months of disease-free time over 48 months (RMST difference: 4.0 months; 95% CI, 0.6-7.9; p = 0.014) and 2.4 months over 36 months (RMST difference: 2.4 months; 95% CI, 0.2-4.7; p = 0.024). The hazard ratio from overlap-weighted Cox regression with covariate adjustment was 0.37 (95% CI 0.09-1.45; p = 0.154), directionally consistent with the RMST findings but not reaching statistical significance. Hazard ratio estimates were directionally consistent across sensitivity analyses but varied in statistical significance, likely reflecting limited power: unadjusted (HR 0.23; p = 0.019), stabilized weighting with covariates (HR 0.19; p = 0.046), and multivariable adjustment (HR 0.44; p = 0.249).

In this real-world cohort, oral fluoropyrimidines were associated with 4.0 fewer months of disease-free time compared with FOLFOX at 48 months among patients for whom both treatment options were appropriate. As a single-center study with limited events, these findings should be confirmed in larger multicenter cohorts. The combination of RMST with overlap weighting provides an interpretable framework for comparative effectiveness questions where treatment selection is strong.