10-Year Results of MOSAIC Trial Show Continued Survival Benefit of Adjuvant FOLFOX4 in Stage III Colon Cancer


Key Points

  • At 10 years, FOLFOX4 was associated with improved overall survival among all patients (stage II and III disease population) and among those with stage III disease.
  • There appeared to be a survival benefit of FOLFOX4 in both patients with mismatch repair–deficient tumors and those with BRAF mutation.

Ten-year results of the MOSAIC trial, reported in the Journal of Clinical Oncology by André et al show a continued overall survival benefit with adjuvant FOLFOX4 (fluorouracil [5-FU] leucovorin plus oxaliplatin) vs 5-FU/leucovorin in patients with stage III colon cancer and in the entire population of patients with stage II or III disease, but no benefit in patients with stage II disease. In analysis of a subgroup of patients with available samples, FOLFOX4 appeared to improve survival in both patients with BRAF mutation and in those with mismatch repair–deficient tumors.

Survival Rates

In MOSAIC, patients with stage II or III disease were randomly assigned to receive adjuvant FOLFOX4 or 5-FU/leucovorin. After a median follow-up of 9.5 years, 10-year overall survival among all 2,246 patients was 71.7% in the FOLFOX4 group vs 67.1% in the 5-FU/leucovorin group (hazard ratio [HR] = 0.85, P = .043), 78.4% vs 79.5% in those with stage II disease (HR = 1.00, P = .980), and 67.1% vs 59.0% in those with stage III disease (HR = 0.80, P = .016).

In patients with high-risk stage II disease defined as T4, tumor perforation, or fewer than 10 lymph nodes examined, estimated 10-year overall survival was 75.4% vs 71.7% (P = .058). The absolute survival benefit associated with FOLFOX4 treatment among all patients increased from 2.2% at 6 years to 4.76% at 10.

Analysis by Mismatch Repair and BRAF Status

Mismatch repair deficiency and BRAF mutation status were assessed in 1,008 patients with formalin-fixed paraffin-embedded specimens. Among these, 9.4% had mismatch repair–deficient tumors and 10.4% had BRAF mutation.

Mismatch repair–deficient (HR = 2.02, P = .014) but not BRAF mutation (P = .965) was an independent prognostic factor for overall survival. FOLFOX4 was associated with a trend toward improved survival both among patients with mismatch repair deficiency (HR = 0.41, 95% confidence interval [CI] = 0.16–1.07) and among those with BRAF mutation (HR = 0.66, 95% CI = 0.31–1.42).   

The investigators concluded: “The [overall survival benefit] benefit of oxaliplatin-based adjuvant chemotherapy, increasing over time and with the disease severity, was confirmed at 10 years in patients with stage II to III colon cancer. These updated results support the use of FOLFOX in patients with stage III disease, including those with [mismatch repair–deficient] or BRAF mutation.”

Thierry André, MD, of Hôpital St Antoine, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by Sanofi, Genomic Health, and GERCOR. For full disclosures of the study authors, visit

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