Clinical Summary: 

•  Jaafar Bennouna, MD, PhD, discusses results from the phase 3 IROCAS trial comparing adjuvant mFOLFIRINOX with mFOLFOX6 in patients with R0-resected high-risk stage III colon adenocarcinoma, defined by pT4 and/or pN2 disease.
• Adjuvant mFOLFIRINOX did not significantly improve 3-year disease-free survival compared with mFOLFOX6 (65.6% vs 66.3%; HR, 1.07), while overall survival data remained immature and severe diarrhea and fatigue were more frequent with the intensified regimen.
• These findings reinforce the role of oxaliplatin-based doublet chemotherapy in high-risk stage III colon cancer and highlight the need for novel adjuvant strategies beyond chemotherapy intensification based on TNM stage alone.

Jaafar Bennouna, MD, PhD,  Hôpital Foch, Suresnes, France, discusses results from an academic randomized phase 3 trial evaluating adjuvant mFOLFIRINOX versus mFOLFOX6 in patients with R0-resected high-risk stage III colon cancer, following his presentation at the European Society for Medical Oncology (ESMO) Congress 2026.

Dr Bennouna reviews the absence of a significant disease-free survival benefit with intensified adjuvant chemotherapy, including findings across prespecified clinical subgroups. He also discusses the immature overall survival findings, increased rates of severe diarrhea and fatigue with mFOLFIRINOX, and the importance of developing more effective adjuvant treatment strategies beyond pathologic risk-based intensification. 

Transcript: 

Hello, Jaafar Bennouna, I am a medical oncologist working at Hôpital Foch, Suresnes, France. Today at the ESMO meeting, I presented the results of the IROCAS study.

The IROCAS study is a randomized phase 3 trial conducted in patients with high-risk stage III colon cancer. The question is, is pathological risk sufficient to guide adjuvant treatment intensification?

When I talk about treatment intensification, the goal is to know what is the efficacy of FOLFIRINOX for these patients with high pathological risk. For that, we conducted an academic phase 3 trial randomizing 1:1 FOLFIRINOX with irinotecan (180 mg/m²) and no bolus of 5-FU, and modified FOLFOX6.

This study was conducted in France, Canada, and Italy. Patients with resected colon adenocarcinoma have a high risk of recurrence, meaning that it was pT4 and/or pN2 disease. Baseline characteristics were well balanced between the two arms. The median age was 58 years old, and more than 80% of patients had an ECOG performance status of 0.

Unfortunately, there was no difference for the primary end point. The primary end point was the 3-year disease-free survival. FOLFIRINOX, 65% for 3-year disease-free survival, FOLFOX6, 66% for 3-year disease-free survival (HR, 1.07; P = .61). Same picture for overall survival, 3-year overall survival, 91.2% for FOLFIRINOX versus 86.7% for FOLFOX6 (HR, 0.85; P = .37). There was no new signal in terms of efficacy, and there was no benefit in prespecified subgroups. In particular, no benefits for pT4, pN2, or tumor location.

The conclusion of IROCAS is that simply escalating conventional cytotoxic therapy according to pathological risk alone is unlikely to be the way forward. High pathological risk defines patients who need a better outcome, but it does not tell us how to achieve them. The standard for high-risk pT4 and/or pN2 disease with resected colon carcinoma is always FOLFOX6 for 6 months, according to the results of the IDEA trial.

Source: 

Bennouna J, Andre T, O’Callaghan C, et al. 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. Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA29.