Oxaliplatin/5FU/LV in adjuvant colon cancer: Updated efficacy results of the MOSAIC trial, including survival, with a median follow-up of six years Authors: Gramont et al. Reviewer: Dr Phil Bedard Date posted: June 21, 2007

Background MOSAIC trial –Primary endpoint = DFS Advantage in 3-yr and 5-yr DFS for FOLFOX4 compared with LV5FU2 in Stage II or III colon cancer –Secondary endpoint = OS, safety

Patients with resected Stage II or Stage III colon cancer N=2246 LV5FU2 Leucovorin 200mg/m2 IV over 2 hours 5-FU 400mg/m2 IV over 2 hours, then 600mg/m2 continuous IV infusion over 22 hours days 1 and 2 N=1123 FOLFOX4 Leucovorin 200mg/m 2 IV over 2 hours 5-FU 400mg/m2 IV over 2 hours, then 600mg/ m 2 continuous IV infusion over 22 hours days 1 and 2 Oxaliplatin 85mg/m 2 IV N=1123 Study Design

Results: 6-yr OS FOLFOX4LV5FU2HRp-value Overall ( )0.057 Stage II ( )0.996 High Risk Stage II Not presented Not Presented 0.93 ( ) (estimated from graph presented) Stage III ( )0.029 High-risk stage II- defined as at least one of the following: T4, tumor perforation, bowel obstruction, poorly differentiated tumor, venous invasion, <10 lymph nodes examined 5 Yr DFS HR 0.74 ( ) 5 yr DFS 82.1 % (FOLFOX 4 vs 74.9% LV5FU2)

Results Incidence of peripheral neuropathy at 4 years in FOLFOX 4 arm Grade 1: 12.0% Grade 2: 2.8% Grade 3: 0.7%

Study Commentary There is an OS benefit for Stage III patients with FOLFOX4 DFS but no OS survival benefit in high risk stage II patients –There may not have been power to detect a survival benefit in this subset of patients –? Meta analysis possible with patients from NSABP C07 Although there is evidence of recovery from peripheral neuropathy, –15% of patients had neuropathy at 4 years –< 1 % have grade 3 neuropathy at 4 yrs

Bottom Line for Canadian Medical Oncologists Adjuvant FOLFOX4 improves DFS and OS in resected stage III colon cancer ? Role of FOLFOX4 in high risk stage II There is no role for FOLFOX4 in low-risk stage II colon cancer Patients should be warned about the risk of persistent neuropathy with oxaliplatin