A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon:
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Transcript of A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon:
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A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon:Survival results of NSABP Protocol C-07
N. Wolmark, S. Wieand, P. J. Kuebler, L. Colangelo, M. J. O'Connell, G. Yothers
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Disclosure:Norman Wolmark is an
unpaid member of Sanofi-Aventis advisory boards
50 YEARSProtocol C-07
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NSABP C-07
Stage ll + lll
FLOXFULV
Randomize
Strat: # Pos. N
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FU B RestLV 500
FU 500 B
RestLV 500 2hr
OHP 8585 2hr2hr
500
Week 1 2 3 4 5 6 7 8
R
NSABP C-07
2hr
x3
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NSABP C-07Opened: 02-00Closed: 11-02Accrual: 2492
MFU: 34 mo 5’05MFU: 42.5 mo 6’07MFU: 67 mo
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C-07Accrual
FULV FLOX
Randomized
Inelig/No F-U
Analysis
1245
36
1209
1247
47
1200
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NSABP C-07
Primary Endpoint: DFS
Event: first recurrence, second primary, death (any cause)
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NSABP C-07
Secondary Endpoint: Overall Survival
Formal analysis of survival: 5 years after the last patient was entered (11’02)
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Consequently the power to detect the protocol specified 0.214 reduction in the annual death rate was decreased from 0.89 to 0.81.
Expected # deaths: 700Actual # deaths: 560
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C-07Patient Characteristics
Pos Nodes FULV % FLOX %
01-3≥4
28.9 45.825.3
28.8 45.325.8
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DFS Update
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p = 0.002HR: 0.81 [0.70 – 0.93]
19% risk reduction
C-07 DFS
3y 5yFLOX 76.1% 69.4%FULV 71.5% 64.2% Δ 4.6% 5.2%
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≥ 65 yr
Overall
< 65 yr
N 0
1-3
>3
FLOX Better FULV Better
DFS Hazard Ratio
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Overall Survival
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D(n) 5y 6yFLOX 259 80.3% 77.7%FULV 301 78.3% 73.5% Δ 42 2.0% 4.2% p = 0.06HR: 0.85 [0.72 – 1.01]
15% risk reduction
C-07 Survival
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≥ 65 yr
Overall
< 65 yr
Stage II
Stage III
S Hazard Ratio
FLOX Better FULV Better
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5y S Δ HR
C-07 80.3 % 2.0 % 0.85
Mosaic 81.3 % 2.2 % 0.85
C-07 and Mosaic oxaliplatin benefit
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Is 5 years the appropriate time to assess overall
survival?
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P<0.0001
ACCENT Survival After Recurrence
O’Connell JCO May 2008
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1978-19851986-19921993-1999
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Median C-04 ‘89 12.7C-05 ’91 12.6C-06 ’97 16.4C-07 ’00 19.6
P < 0.0001 N~8000
C-04 - C-07 Survival after Recurrence
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Median FLOX 17.6 FULV 22.2
P = 0.02HR: 1.24
C-07 Survival after Recurrence
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ConclusionsThere is a trend toward improved survival (p=0.06) with the addition of oxaliplatin to weekly FULV at 67m MFU
The benefit of oxaliplatin (S and DFS) is independent of the schedule of FULV administration
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ConclusionsThe durable consistency between the results of C-07 and Mosaic validates the benefit of oxaliplatin
Longer follow-up (>5 yrs) in future colon adjuvant trials appears to be appropriate to reliably detect survival benefit
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H. Samuel Wieand
February 19, 1944 - June 10, 2006