Tonight’s speakers: Dr. Dan Sargent and Kim Ryan Disclaimer: “This Report is not an official event of the 2012 Gastrointestinal Cancers Symposium. Not sponsored or endorsed by any of the cosponsoring organizations of the 2012 Gastrointestinal Cancers Symposium.”

1. Welcome!
Report from GI Cancer Symposium 2012
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3. Fight Colorectal Cancer
1. Tonight’s speakers: Dr. Dan Sargent and Kim Ryan
2. Archived webinars: Link.FightCRC.org/Webinars
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pin when you tell us how we did tonight.
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Disclaimer
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5. Fight Colorectal Cancer
Cheat sheet
AE ~ Adverse Event
BSC ~ Best Supportive Care
CAPOX ~ (also called XELOX) Capecitabine and Oxaliplatin
DCR ~ Disease Control Rate
FOLFOX ~ 5FU/Leucovorin, Oxaliplatin
KRAS WT ~ Kristen Rat Sarcoma/Wild Type
mCRC ~ Metastatic Colorectal Cancer
MSI ~ Microsatellite Instability
OS ~ Overall Survival
ORR ~ Overall Response Rate
PET ~ Positron Emission Tomography
Pt/Pts ~ Patient/Patients
PFS ~ Progression Free Survival
QOL ~ Quality of Life
SD ~ Stable Disease

6. Fight Colorectal Cancer
Dr. Daniel Sargent, PhD
Mayo Clinic Cancer Center
Biostatistician for the gastrointestinal research program at
the Mayo Clinic Cancer Center and is involved in multiple
ongoing clinical trials of both cancer treatment and cancer
screening.

7. Fight Colorectal Cancer
Where have we been and
where are we going?
2007 to 2012
What’s happened in the last
5 years?

8. Fight Colorectal Cancer
GI ASCO 2007
Family members of people with crc have
a high risk of having polyps with the
potential to become cancer
• Increasing the dose of cetuximab (Erbitux®) until a rash
• appeared increased tumor response rates
PET scanning before surgery helps make better
decisions on which pts should have surgery
& improves survival
Patient communications & expectations data were shared
showing more than 1/3 of pts would choose chemotherapy
even if it only improved their chances against a recurrence by 1%

9. Fight Colorectal Cancer
GI ASCO 2012
• Biomarkers (Predictive and Prognostic)
• Elderly patients responses to certain therapies
• Erbitux and Brivanib in combination for refractory
metastatic disease
• Quality of life assessment data presented
• New data for metastatic refractory colorectal cancer
patients

10. Biomarkers
Background ~ 20% of stage II CRC patients will experience a relapse
of their disease, and may benefit from adjuvant chemotherapy
Question ~ How do we determine who those patients are?
The “ColoPrint index” was determined on 320 patients, using gene
expression, fresh tissue, MSI-status, and patient follow-up
Conclusions ~ ColoPrint:
• Available as a diagnostic test with high precision and reproducibility
• Improves the prognostic accuracy of pathological factors and MSI
• Helps to identify low risk patients, who may be safely managed
without chemotherapy
Caveats ~ Requires fresh tissue, still a modest size trial

11. Biomarkers
Background ~ Identifying a prognostic marker would aid in the
management of patients with node negative colon cancer
Question ~ What is the prognostic value of guanylyl cyclase for disease
recurrence in untreated stage II colon cancer?
GCC mRNA was quantified from 310 stage II patients, enrolled in 2
studies between 1991-2006. Patients classified according to their GCC
lymph node ratio.
Clinical outcomes included time to recurrence, overall survival, and
disease free survival
Conclusion ~ Patients with GCC lymph node ratio high risk have
significantly poorer outcomes compared to patients with low risk status.
Caveats ~ Modest size study, limited institutions, validation study ongoing

12. Elderly Patient Population
Background ~ Cross trial comparison of age, comparing 3 trials in
patients with stage III disease
Question ~ What affect does age have on the effectiveness of
Oxaliplatin based adjuvant therapy?
NSABP C-07 MOSAIC NO16968
FLOX FOLFOX XELOX
Age, years <70 >70 <70 >70 <70 >70
DFS
Hazard Ratio 0.76 1.03 ~0.75 0.91 0.8 0.86
OS
Hazard Ratio 0.8 1.18 ~0.77 1.1 0.82 0.91
Conclusion ~ The benefits of adding Oxaliplatin to 5-FU are less in
patients greater than 70 years of age

13. Elderly Patient Population
Background ~ While colon cancer is predominantly a disease of the elderly,
older patients are underrepresented in clinical trials.
Question ~ Do treatment patterns and benefits realized by trial participants
pertain to older patients?
Retrospective analysis of 3390 stage II and stage III patients >66 years old who
received 5FU/LV, FOLFOX, CAP or CAPOX within 3 months after surgery.
Risk of
death
HR 95% CI p-value
5FU/LV 1
FOLFOX 0.7 0.55 - 0.90 0.005
CAP 1.17 0.88 - 1.56 0.293
CAPOX 0.44 0.20 - 0.98 0.044
Conclusion ~ Treatment outcomes for elderly pts were comparable
between CAP based and 5FU/LV-based regimens and consistent with
results reported in randomized clinical trials.

14. Cetuximab + Brivanib
Background ~ Cetuximab has improved overall survival in pts with metastatic, refractory,
KRAS wild type CRC
Question ~ Will the addition of Brivanib, a tyrosine kinase inhibitor targeting vascular
endothelial and fibroblast growth receptors, improve overall survival in a phase III trial?
Phase III trial, of pts with mCRC, previously treated w/combination therapy, randomized:
• CET 400mg/m2 loading dose, followed by weekly 250mg/m2 + 800 mg oral BRIV daily
or placebo
Brivanib Arm Placebo Arm Hazard Ratio
Median OS 8.8 months 8.1 months 0.88
Median PFS 5.0 months 3.4 months 0.72
Partial Response 13.60% 7.20%
Stable Disease 50% 44%
Conclusion ~ Despite positive effects of PFS, the combination of CET and BRIV
did not significantly improve overall survival

15. Cetuximab + Brivanib QOL Data
Background ~ Although the primary endpoint (overall survival) was not
improved, PFS favored the CET + BRIV arm
Question ~ When looking at quality of life as a secondary endpoint, what effect
did the CET + BRIV arm have on QOL?
750 randomized patients were assessable for QOL
Receiving CET 400mg/m2 loading dose, followed by weekly 250mg/m2 + 800
mg PO BRIV daily or placebo
Median time to QOL DET (deterioration)1.6 months vs 1.1 months
Median time to QOL PF (physical function) 5.6 months vs 1.7 months
Conclusion ~ Despite a PFS benefit, the combination of CET + BRIV
worsened time to QOL DET and PF, in pts with refractory KRAS WT mCRC

16. Regorafenib
Background ~ Regorafenib (small molecule), an oral multikinase inhibitor of a
broad range of angiogenic, oncogenic, and stromal kinases, was study in a
Phase 1 trial, and showed results in disease control of 74% in pts with mCRC
who had progressed after all approved therapies
Question ~ In a larger phase III CORRECT trial, what is the efficacy and safety
of regorafenib in this difficult to treat patient population?
Phase III, 760 patients randomized 2:1 to receive regorafenib 160mg orally, 3
wks on, 1 wk off, + BSC or placebo
Regorafenib Placebo HR
Median OS 6.4 months 5.0 months 0.77
Median PFS 1.9 months 1.7 months 0.49
ORR 1.60% 0.40%
SD 43.80% 14.90%
DCR 44.80% 15.30%

17. Regorafenib (con’t)

18. Regorafenib (con’t)

19. Regorafenib (con’t)
Affect did not differ by KRAS status
Most frequent grade 3 adverse events in the regorafenib arm:
Hand foot reaction 16%
Fatigue 9%
Diarrhea 7%
Hypertension 7%
Conclusion ~ Statistically significant benefit in OS and PFS was
observed for regorafenib over placebo in patients with mCRC who
have failed all approved standard therapies. No new or unexpected
safety signals were found.

20. Conclusions
• Biomarkers will be key to treating stage II (and perhaps
stage III) patients, as we know many patients do not
need treatment
• Less intensive therapy an appropriate option for elderly
patients
• Benefit in PFS may not be sufficient to truly benefit the
patient
• Regorafenib provides modest benefit in last line setting,
but clearly worthy of further study in earlier lines of
therapy

21. Fight Colorectal Cancer

22. Fight Colorectal Cancer
Upcoming Webinar
“The Importance of Diet, Exercise & Nutrition:
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March 21, 2012
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23. Fight Colorectal Cancer
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