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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 BedardDate posted: June 21, 2007

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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

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Patients with resected Stage II or Stage III

colon cancerN=2246

LV5FU2Leucovorin 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

FOLFOX4Leucovorin 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 2Oxaliplatin 85mg/m2 IV

N=1123

Study Design

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Results: 6-yr OS

FOLFOX4 LV5FU2 HR p-value

Overall 78.6 76.0 0.85 (0.72-1.01) 0.057

Stage II 86.8 86.9 1.00 (0.72-1.41) 0.996

High Risk Stage II

Not presented

Not

Presented

0.93 (0.6 -1.4)

(estimated from graph presented)

Stage III 73.0 68.6 0.80 (0.66-0.98) 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 (0.52-1.06)5 yr DFS 82.1 % (FOLFOX 4 vs 74.9% LV5FU2)

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Results

• Incidence of peripheral neuropathy at 4 years in FOLFOX 4 arm

• Grade 1: 12.0% • Grade 2: 2.8% • Grade 3: 0.7%

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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

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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