MOSAIC
25
MOSAIC Stage ll+lll FOLFOX4 LV5FU2 Randomize
description
MOSAIC. Randomize. Stage ll+lll. FOLFOX4. LV5FU2. DFS. 3-year. FOLFOX (n=1123) 77.9% LV5FU2 (n=1123) 72.8%. Hazard ratio: 0.77 [0.65 – 0.92] p < 0.01. DFS (months). 23 % risk reduction in the FOLFOX arm. On November 4, 2004, the FDA - PowerPoint PPT Presentation
Transcript of MOSAIC
MOSAIC
Stage ll+lll
FOLFOX4LV5FU2
Randomize
0.5
0.6
0.7
0.8
0.9
1
0 10 20 30 40 50
DFS
DFS (months)
Hazard ratio: 0.77 [0.65 – 0.92] p < 0.01
FOLFOX (n=1123) 77.9%LV5FU2 (n=1123) 72.8%FOLFOX (n=1123) 77.9%LV5FU2 (n=1123) 72.8%
23 % risk reduction in the FOLFOX arm
3-year
On November 4, 2004, the FDA approved oxaliplatin in combination with infusional FULV for adjuvant stage III colon cancer. The approval was based on improvement in DFS…
NSABP C-07
Stage ll + lll
FLOXFULV
Randomize
Strat: # Pos. N
FU Rest
LV 500
FU 500
RestLV 500
OHP 8585 2hr2hr
500
Week 1 2 3 4 5 6 7 8
R
NSABP C-07
x3
NSABP C-07
Opened: 02-00Closed: 11-02Accrual: 2407
MTS: 34 mo.
NSABP C-07
Endpoint: 3 yr DFS
Event: first recurrence, second primary, death (any cause)
NSABP C-07
89% power to detect: 5.4% ↑ DFS.
C-07Accrual
FULV FLOX
Randomized
Inelig/Lost
Analysis
1245
38
1207
1247
47
1200
C-07Patient Characteristics
FULV % FLOX %
< 60
60-69
70+
50.4
33.0
16.6
52.431.9
15.7
Age
C-07Patient Characteristics
FULV % FLOX %
Left ColonRight ColonSigmoidMultiple + Unk
20.841.536.8
1.9
19.845.732.6
1.9
Location
C-07Patient Characteristics
Pos Nodes FULV % FLOX %
01-3≥4
28.8 45.725.3
28.9 44.825.6
C-07Overall Toxicity (%)
0-2345
FULV FLOX
4941
91
385010
1
Grade
C-07 Sanofi-NCI Neurotoxicity
Gr 1. P/D that do not interfere with functionGr 2. P/D interfering with function, but not ADLGr 3. P/D with pain or interference with ADLGr 4. Persistent PD that are disabling or life-threatening
85.4
29.4
0
20
40
60
80
100
DuringTx 12 months
Gr >1 (All) Neurotoxicity (%)
8
0.5
0
2
4
6
8
10
DuringTx 12 months
Gr 3 Neurotoxicity (%)
OxaliplatinProtocol-stipulated
cumulative dose
C-07 765 mg/m2
Mosaic 1020 mg/m2
86.9
68.662.5
0
10
20
30
40
50
60
70
80
90
100
1 2 3
% of full dose oxaliplatin /cycle
73% received protocol-stipulated cumulative dose
C-07Bowel wall injury
FULV
FLOX
34 (2.7%) 56 (4.5%)
N
Smith R ASCO GI #195,2004
C-07Deaths during treatment
FULV
FLOX
14 (1.1%)
15 (1.2%)
N
Ev # 3yr DFSFLOX 272 76.5%FULV 332 71.6%
p < 0.004HR: 0.79 [0.67 – 0.93]
21 % risk reduction
C-07 DFS
0.5
0.6
0.7
0.8
0.9
1
0 1 2 3 4
The global test for interaction between treatment and
tumor stage (II+III) was not significant (p=0.70)
3y DFS Δ HR
C-07 76.5 % 4.9 % 0.79
Mosaic 77.9 % 5.1 % 0.77
C-07 and Mosaic OXA benefit
Conclusions
The addition of oxaliplatin to weekly bolus FULV significantly improves 3-year DFS in patients with Stage II and III colon cancer
The data confirm and extend the results of the Mosaic trial
ConclusionsThe benefit of oxaliplatin does not appear to be dependent on the schedule of FULV administration
The data support the use of weekly bolus FULV in combination with oxaliplatin in adjuvant colon cancer
