MOSAIC trial

Background

Phase III randomized trial in 2246 patients with completely resected stage II or III colon cancer. Tested whether adding oxaliplatin to bolus/infusional 5-FU/leucovorin (FOLFOX4) improves disease-free survival as adjuvant therapy.

Interventions and follow up

Arm A: FOLFOX4 (oxaliplatin 85 mg/m2 plus LV 200 mg/m2, 5-FU 400 mg/m2 bolus then 600 mg/m2 22-h infusion, D1-2) every 14 days x 12 cycles
Arm B: 5-FU/LV alone (same LV5FU2 schedule) every 14 days x 12 cycles
Primary endpoint: 3-year disease-free survival (DFS)
Median follow-up: 37.9 mo (primary analysis)

Results

3-yr DFS (overall): 78.2% with FOLFOX4 vs 72.9% with 5-FU/LV (HR 0.77, 95% CI 0.65-0.91, P=.002)
Stage III subgroup: HR 0.76, 95% CI 0.62-0.92
Stage II subgroup: HR 0.80, 95% CI 0.56-1.15 (not significant)

Adverse events

Hematologic: Grade ≥3 neutropenia 41.1% vs 4.7%; febrile/infected neutropenia only 1.8% vs 0.2%
Neurologic: Any-grade peripheral sensory neuropathy 92.1%, grade 3 in 12.4%; persisted at 1 year in 1.1%
GI: Grade ≥3 events more frequent overall with FOLFOX4 (diarrhea, nausea/vomiting)

Conclusions

Adjuvant FOLFOX4 significantly improved disease-free survival versus 5-FU/LV in resected stage II-III colon cancer, with benefit driven predominantly by stage III disease, establishing oxaliplatin-based adjuvant therapy as standard.

Key Limitations

Stage II benefit was not statistically significant, and routine use in stage II remains controversial absent high-risk features. Oxaliplatin-induced sensory neuropathy can be long-lasting. Conducted before MMR/MSI status routinely guided stage II decisions.

Clinical Context

MOSAIC established FOLFOX as standard adjuvant therapy for stage III colon cancer; FDA approved oxaliplatin in the adjuvant setting in 2004. 6-year OS analysis later confirmed survival benefit in stage III. ESMO guidelines recommend oxaliplatin-based adjuvant chemotherapy for stage III; the IDEA collaboration subsequently informed 3- vs 6-month duration.

References