A randomised phase III trial of adjuvant treatment intensification with mFOLFIRINOX versus mFOLFOX6 in high-risk stage III colon cancer: Results of the international IROCAS study
In brief
mFOLFIRINOX fails to improve 3-year disease-free survival in high-risk colon cancer
In 795 patients with high-risk stage III colon cancer, 3-year disease-free survival was 65.6% with mFOLFIRINOX and 66.3% with mFOLFOX6, showing no benefit from the more intensive regimen. Severe side effects overall were similar, but diarrhea and fatigue were more frequent with mFOLFIRINOX; longer follow-up is needed for survival outcomes.
- Journal
- Annals of oncology : official journal of the European Society for Medical Oncology (Q1)
- Published
- 25 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- J Bennouna, T André, E Martin, C Cremolini, S Gill, T Asmis, et al.
- PMID
- 42927853
- DOI
- 10.1016/j.annonc.2026.10.104
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 1 November 2026): Phase III trial tests adjuvant chemotherapy intensification in high-risk colon
Abstract
BACKGROUND: Patients with pT4 and/or pN2 stage III colon cancer remain at high risk of recurrence despite oxaliplatin-based adjuvant chemotherapy. We evaluated whether intensification with modified FOLFIRINOX improved outcomes compared with modified FOLFOX6. PATIENTS AND METHODS: In this international, academic, open-label, randomised phase III trial conducted by PRODIGE in France, CCTG in Canada, and GONO in Italy, patients with stage III colon adenocarcinoma after R0 resection presenting T4 and/or N2 were randomly assigned (1:1) to mFOLFIRINOX or mFOLFOX6 every 2 weeks for 12 cycles. The primary endpoint was 3-year disease-free survival (DFS) in the intention-to-treat population. RESULTS: Between May 2017 and June 2023, 795 patients were assigned to mFOLFIRINOX (n=398) or mFOLFOX6 (n=397). Median age was 59 years (range 19-75); 39.7% were women, 52.8% had pT4 disease, 72.2% had pN2 disease, and 25.3% had both. At a median follow-up of 55 months (IQR 42.6-65.9), 284 DFS events had occurred: 146 with mFOLFIRINOX and 138 with mFOLFOX6. Three-year DFS was 65.6% versus 66.3%, respectively (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.84-1.36; P=0.61). Although Overall survival (OS) data remain immature, 3-year OS was 91.2% versus 86.7% (HR 0.85, 95% CI 0.61-1.21; P=0.37); no significant treatment-by-subgroup interaction was observed. Grade ≥3 adverse events occurred in 62.2% and 62.1% of patients, respectively. Grade ≥3 diarrhoea (15.6% versus 3.8%) and fatigue (7.3% versus 1.8%) were more frequent with mFOLFIRINOX, whereas grade ≥3 neutropenia was less frequent (18.0% versus 23.9%). G-CSF use was 37.8% versus 19.1%. CONCLUSION: Adjuvant mFOLFIRINOX triplet chemotherapy did not improve DFS compared with standard doublet mFOLFOX6 in patients with high-risk stage III colon cancer. These findings do not support empirical chemotherapy intensification and highlight the need for novel adjuvant strategies. GOV IDENTIFIER: NCT02967289.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.