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