IROCAS: A randomized phase III trial of adjuvant treatment intensification with mFOLFIRINOX versus mFOLFOX6 in high-risk stage III (T4 and/or N2) colon cancer

doi:10.1016/j.annonc.2026.10.104

IROCAS

Patient / Population Intervention / Exposition Vergleich Endpunkt

In patients with high-risk stage III colon cancer, adjuvant mFOLFIRINOX did not improve 3-year disease-free survival compared with mFOLFOX6.

N

795Patienten

Design

Academic phase III trial randomising 795 patients with R0-resected pT4 and/or N2 colon adenocarcinoma 1:1 to adjuvant mFOLFIRINOX or mFOLFOX6 every 2 weeks for 12 cycles (NCT02967289).

Endpunkt

3-year disease-free survival, analysed in the intent-to-treat population.

ErgebnisThree-year DFS 65.6% with mFOLFIRINOX vs 66.3% with mFOLFOX6 (HR 1.07, 95% CI 0.84-1.36; P = 0.61), with 284 DFS events (146 vs 138) at a median follow-up of 55 months. Three-year OS 91.2% vs 86.7% (HR 0.85, 95% CI 0.61-1.21; P = 0.37); OS data remain immature. Grade ≥3 adverse events 62.2% vs 62.1%, grade ≥3 diarrhoea 15.6% vs 3.8%, grade ≥3 fatigue 7.3% vs 1.8% and grade ≥3 neutropenia 18.0% vs 23.9%. G-CSF use 37.8% vs 19.1%.

Bennouna J, André T, Martin E, et al. Annals of Oncology. 2026. 10.1016/j.annonc.2026.10.104

Diskussion & Kritik

In this randomised phase III trial, adding intensity with mFOLFIRINOX did not improve 3-year DFS over mFOLFOX6 after a median follow-up of 55 months, with a hazard ratio close to 1; the abstract gives no sample-size calculation or prespecified margin, and the confidence interval does not rule out a modest effect in either direction. The arms differ by more than irinotecan, since the mFOLFIRINOX regimen also omitted the 5-FU bolus given with mFOLFOX6, so the trial compares two regimens rather than a single added drug. The OS difference was not statistically significant and the data are immature, so no survival conclusion can be drawn, while overall grade ≥3 toxicity was similar but diarrhoea, fatigue and G-CSF use were higher with mFOLFIRINOX. The abstract does not report blinding, treatment exposure or dose intensity, and patients were selected by TNM stage alone.