Fight Colorectal Cancer’s Medical Advisory Board Member, Axel Grothey, MD, focused this webinar to stage III colon cancer patients. Dr. Grothey, medical oncologist at Mayo Clinic, will spend the hour discussing current treatment options and exciting new research that pertains to stage III colon cancer patients.

1. Treatment Options for Stage III
Colon Cancer
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2. • Speaker: Axel Grothey, MD
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5. Speaker:
Axel Grothey, MD, is a consultant in the Division of Medical Oncology,
Department of Oncology, at Mayo Clinic. He holds the academic rank of
professor of oncology in Clinical and Translational Science at Mayo Graduate
School. He is a member of Mayo Clinic’s Cancer Center.
Dr. Grothey’s clinical interests focus on gastrointestinal cancers, in particular,
colorectal cancer, anti-angiogenesis, signal transduction inhibitors, and clinical
trial design and statistics. As a consultant and investigator, his research has been
funded by the National Cancer Institute (NCI)and the National Institutes of
Health, among other organizations. Dr. Grothey serves in journal review and
editorial activities for numerous medical journals and is editor for Clinical
Colorectal Cancer, Emerging Cancer Therapeutics, Practice Update Oncology,
and Therapeutic Advances in Medical Oncology. In educational activities, he
has served as a teacher, and he is a five-time recipient of Teacher of the Year
recognition at Mayo Clinic. Dr. Grothey has given numerous international,
national and regional presentations, as well as invited and visiting professor
presentations. He has co-authored more than 500 articles, books, book chapters,
editorials, abstracts, and letters.

6. Prospective Pooled Analysis of Six Phase III
Trials Investigating Duration of Adjuvant
Oxaliplatin-based therapy (3 vs 6 months) for
Patients with Stage III Colon Cancer:
The IDEA (International Duration Evaluation of
Adjuvant Chemotherapy) Collaboration
Qian Shi, Alberto F. Sobrero, Anthony F. Shields, Takayuki Yoshino, James Paul, Julien Taieb,
Ioannis Souglakos, Rachel Kerr, Roberto Labianca, Jeffrey A. Meyerhardt, Franck Bonnetain,
Toshiaki Watanabe, Ioannis Boukovinas, Lindsay A. Renfro, Axel Grothey, Donna Niedzwiecki,
Valter Torri, Thierry Andre, Daniel J. Sargent, Timothy Iveson

7. Background and Rationale
• Current standard of care for stage III colon cancer patients:
6 months of oxaliplatin-based adjuvant therapy with FOLFOX or CAPOX
(XELOX)
• Oxaliplatin is associated with cumulative dose-dependent neurotoxicity
• Debilitating for many patients, both short- and long-term
– Nerve damage (e.g. numbness, tingling, pain) can persist long after
discontinuation of therapy, sometimes permanently
• Dose reductions and early discontinuation of therapy are common
• Shorter duration treatment without loss of efficacy would be of benefit to
patients and health care resources
Presented by: Qian Shi, PhD on behalf of IDEA collaborators

8. International Duration Evaluation of Adjuvant
Chemotherapy (IDEA) Collaboration
Presented by: Qian Shi, PhD on behalf of IDEA collaborators
• Academic collaboration of clinicians and statisticians from six
randomized phase III trials (12 countries)
– SCOT (UK, Denmark, Spain, Australia, Sweden, New Zealand),
TOSCA (Italy), Alliance/SWOG 80702 (US, Canada), IDEA France,
ACHIEVE (Japan), HORG (Greece)
• Total of 12,834 patients with stage III disease included in analysis
– High number of patients needed to make sure with high confidence
that we are not sacrificing efficacy of therapy for decreased toxicity

9. Presented by:

10. Balancing Less Toxicity and
Maintained Efficacy
Which
difference is
acceptable?

11. Stage III Colon Cancer
Presented by: Jeffrey Meyerhardt, MD, MPH

12. Stage III Colon Cancer
Cured with Surgery Alone
Didn’t need chemo
Presented by: Jeffrey Meyerhardt, MD, MPH

13. Stage III Colon Cancer
Recur despite surgery
and chemo
Chemo didn’t help
(at least enough)
Presented by: Jeffrey Meyerhardt, MD, MPH

14. Stage III Colon Cancer
Cured because they got adjuvant
therapy after surgery
Only ones that benefit from
chemo (as measured by cure)
Fluoropyrimidine
FOLFOX/CAPOX
Presented by: Jeffrey Meyerhardt, MD, MPH

15. Stage III Colon Cancer
These people all get side
effects from chemotherapy
The 3 trials today and IDEA
collaboration goal is to reduce
side effects, burdens of
therapy, and costs for all
these patients
Presented by: Jeffrey Meyerhardt, MD, MPH

16. Study Overview
• Objective:
Reduce side-effects of therapy
without giving up (too much) anti-
cancer efficacy of therapy
• Non-inferiority design:
As agreed upon by patient advocates and
oncologists, shorter duration of therapy
should not sacrifice more than 12% of
benefit of adjuvant therapy
In statistical terms: upper 95% confidence
interval of Hazard Ratio (HR) of disease free
survival (DFS) should not exceed 1.12
Presented by: Qian Shi, PhD on behalf of IDEA collaborators
Stage III
Colon
Cancer
Patients
R
3 months
6 months
FOLFOX*
or CAPOX*
*Investigator’s choice, no
randomization
12,834 patients

17. Outcomes (all patients)
Regimen
Neurotox G2+
3 mos
arm
6 mos
arm
FOLFOX 17% 48%
CAPOX 15% 45%
Toxicity
P<0.0001
3m duration much less toxic

18. SCOT

19. 0 1 2 3 4 5 6
Years from Randomization
0
10
20
30
40
50
60
70
80
90
100
6 Months
3 Months
Duration
0 1 2 3 4 5 6
Years from Randomization
0
10
20
30
40
50
60
70
80
90
100
PercentWithoutEvent
6 Months
3 Months
Duration
6424 5446 4464 3000 1609 826 321
6410 5530 4477 3065 1679 873 334
Primary Outcomes Analysis
Presented by: Qian Shi, PhD on behalf of IDEA collaborators
Duration 3-yr DFS
3m 74.6 %
6m 75.5 %
3-yr DFS diff. = -0.9%,
95% CI, (-2.4 to 0.6%)
N Patients
At risk
DFS HR = 1.07
95% CI, 1.00 to 1.15

20. Subgroup Analyses
Subgroup
3 year DFS rate (%)
Interpretation
3 months arm 6 months arm
Risk of recurrence
Low-risk ~60%
(T1-3N1)
83.1 83.3
3 months duration
appropriate for low-
risk groupHigh-risk ~40%
(T4 or N2)
62.7 64.4
Regimen
FOLFOX ~60% 73.6 76.0
If CAPOX preferred,
3 months duration
appropriate
independent of stageCAPOX ~40% 75.9 74.8
∆ -0.2
∆ -1.7
∆ -2.4
∆ +1.1
Presented by: Qian Shi, PhD on behalf of IDEA collaborators

21. IDEA Consensus: Risk-based approach to
adjuvant chemotherapy in stage III colon cancer
Presented by: Qian Shi, PhD on behalf of IDEA collaborators
Risk group Recommended duration of adjuvant therapy
T1-3 N1
T4 and/or N2
3 months
Duration of therapy determined by
- tolerability of therapy
- patient preference
- assessment of risk of recurrence
- Regimen (CAPOX vs FOLFOX)
6 months
(~60% of stage III)
(Or other high-risk factors)

22. Conclusions
• IDEA data provide a framework for discussions on risks and benefits of
individualized adjuvant therapy approaches
• Shorter duration of therapy associated with remarkable reduction in
(neuro)toxicity
• For low-risk cancers (~60% of stage III) 3 months duration of
oxaliplatin-based therapy is adequate
– Applies to about 20,000 patients per year in the US
• Yet unexplained finding that shorter duration of CAPOX is adequate,
whereas for FOLFOX a longer duration might be required, in particular,
in high-risk cancers
– No direct comparison between FOLFOX and CAPOX possible!

23. Notable Facts
• IDEA represents an international academic
collaboration conducted over more than a decade
• By far largest prospective study conducted in the
history of colorectal cancer research
• No commercial funding to support these practice-
changing efforts, individual studies were supported
by public funds and philanthropy

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