1. IDEA: Pooled Analysis of Adjuvant Oxaliplatin for 3 vs 6 Mos in Stage III Colon Cancer
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. IDEA: Background
Standard of care in stage III CC: 6 mos with oxaliplatin-based tx (FOLFOX4/modified FOLFOX6, CAPOX)[1]
Neurotoxicity associated with cumulative oxaliplatin dose[2]
Grade 3 PN observed in 12.5% of pts treated with FOLFOX for 6 mos[3]
Reduced treatment duration without efficacy loss would benefit pts and lessen resource usage
IDEA collaboration undertook pooled analysis to determine if adjuvant oxaliplatin-based tx for 3 mos noninferior to 6 mos in pts with stage III CC[4]
CAPOX, capecitabine and oxaliplatin; CC, colon cancer; FOLFOX, leucovorin, fluorouracil, oxaliplatin; PN, peripheral neuropathy; tx, therapy.
1. André T, et al. Curr Colorectal Cancer Rep. 2013;9: Park SB, et al. CA Cancer J Clin. 2013;63: André T, et al. J Clin Oncol. 2009;27: Shi Q, et al. ASCO Abstract LBA1.
Slide credit: clinicaloptions.com

3. IDEA: Trials, Treatment
Prospectively pooled analysis of data from 6 concurrent randomized phase III trials in pts with stage III CC (mITT population: N ≥ 12,834)
Pts randomized 1:1 to 3 vs 6 mos tx with oxaliplatin-based tx (investigator’s choice of FOLFOX or CAPOX)
Trial
Stage III CC Pts, N
Treatment
Country
Median F/u, Mos
Pts on CAPOX, %
TOSCA
2402
CAPOX or FOLFOX4
Italy 62 35
SCOT
3983
CAPOX or mFOLFOX6
Australia, Denmark, New Zealand, Spain, Sweden, UK 37 67
IDEA France
2010
France 51 10
C80702
2440
mFOLFOX6
Canada, US
HORG
708
Greece 48 58
ACHIEVE
1291
Japan 75
CAPOX, capecitabine and oxaliplatin; CC, colon cancer; f/u, follow-up; FOLFOX, leucovorin, fluorouracil, oxaliplatin; mFOLFOX, modified FOLFOX; tx, therapy.
Slide credit: clinicaloptions.com
Shi Q, et al. ASCO Abstract LBA1.

4. IDEA: Statistical Plan
Primary endpoint: DFS in mITT population*
DFS: time from randomization to earliest date of relapse, secondary colorectal primary tumor, or death
Preplanned subgroup analyses by regimen, risk groups
Statistical analyses
DFS HR for 3 vs 6 mos (2-sided 95% CI) estimated with Cox model stratified by trial
Predefined noninferiority margin for HR < 1.12 (12% increase in relative risk)
Requires 3390 DFS events for 90% power with 1-sided α = 0.025
Predefined noninferiority margin for 3-yr DFS rate difference (3 vs 6 mos): -2.7%
Additional endpoints: treatment compliance, safety
CAPOX, capecitabine and oxaliplatin; DFS, disease-free survival; FOLFOX, leucovorin, fluorouracil, oxaliplatin; mITT, modified intent to treat.
*Received ≥ 1 dose of study drug.
Slide credit: clinicaloptions.com
Shi Q, et al. ASCO Abstract LBA1.

5. IDEA: Pt Characteristics by Tx Duration, Regimen
FOLFOX
CAPOX
3 Mos
(n = 3870)
6 Mos
(n = 3893)
(n = 2554)
(n = 2517)
Median age, yrs 64 65
ECOG PS 0/1,* %
77/22
82/18
81/19
T stage, %
T1-2 T3 T4 13 68 19 14 67 63 24 12 25
N stage, % N1 N2 72 28 73 27 71 29
Reached final planned cycle, % 90 86
CAPOX, capecitabine and oxaliplatin; ECOG, Eastern Cooperative Oncology Group; FOLFOX, leucovorin, fluorouracil, oxaliplatin; PS, performance status; tx, therapy; yr, year.
*1% of FOLFOX-treated pts had ECOG PS 2.
Slide credit: clinicaloptions.com
Shi Q, et al. ASCO Abstract LBA1.

6. IDEA: DFS in mITT Population, Risk Subgroups
Noninferiority of oxaliplatin-based tx for 3 vs 6 mos not proven
DFS HR: 1.07 (95% CI: )
Difference in 3-yr DFS rates: -0.9% (95% CI: -2.4% to 0.6%)
3-yr DFS rate difference of 20% between low risk (T1-3, N1) vs high risk (T4 or N2) subgroups
Risk Group HR
Favors 3 mos
Favors 6 mos
Interaction P Value
DFS, disease-free survival; mITT, modified intent to treat; mos, months; tx, therapy.
T1-3, N1
T4 or N2
.11
0.5 1
1.12
1.5 HR
Slide credit: clinicaloptions.com
Shi Q, et al. ASCO Abstract LBA1. Reproduced with permission.

7. IDEA: DFS by Risk Subgroups and Regimen
Risk Group
Regimen
Favors 3 mos
Favors 6 mos
HR (95% CI)
FOLFOX
CAPOX
Not proven
Noninferior
Inferior
1.10 ( ) 0.85 ( )
1.20 ( )
1.02 ( )
T1-3, N1
T4 or N2
CAPOX, capecitabine and oxaliplatin; DFS, disease-free survival; FOLFOX, leucovorin, fluorouracil, oxaliplatin. HR
1.0
1.12
Noninferiority margin
Slide credit: clinicaloptions.com
Shi Q, et al. ASCO Abstract LBA1. Reproduced with permission.

8. IDEA: Safety AE, % FOLFOX CAPOX 3 Mos 6 Mos P Value* Any event†
Grade 2
Grade 3/4 32 38 57
< .0001 41 24 48 37
Neurotoxicity
Grade ¾ 14 3 16 12 36 9
Diarrhea 11 5 13 7 10
.0117
AE, adverse event; CAPOX, capecitabine and oxaliplatin; FOLFOX, leucovorin,, oxaliplatin.
*For Chi-squared test for trend.
†19 grade 5 events reported.
Slide credit: clinicaloptions.com
Shi Q, et al. ASCO Abstract LBA1.

9. IDEA: Investigator Conclusions
DFS noninferiority of adjuvant oxaliplatin-based tx for 3 vs 6 mos not established in pts with stage III CC
Effect of tx duration on DFS varied by pt risk group and regimen
Trial differences in outcomes potentially due to variability in proportion of pts treated with CAPOX
Investigators suggest further study needed to determine whether differences between regimens due to schedule, delivery methods
Shorter tx associated with greater treatment compliance, much less grade ≥ 2 neuropathy
Investigators recommend risk-vs-benefit approach when selecting duration of adjuvant oxaliplatin-based tx
Low-risk pts (T1-3, N1): 3 mos
High-risk pts (T4, N2, or other high-risk variables): 3-6 mos depending on tolerability, pt preferences, recurrence risk, regimen (FOLFOX vs CAPOX)
CAPOX, capecitabine and oxaliplatin; CC, colon cancer; DFS, disease-free survival; FOLFOX, leucovorin, fluorouracil, oxaliplatin; tx, therapy.
Slide credit: clinicaloptions.com
Shi Q, et al. ASCO Abstract LBA1.

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