Transcript PIK3CA mutation

SAKK 41/13: PIK3CA-Mutations Aspirin Colon Cancer
Prospective, double-blinded, placebocontrolled randomized trial of adjuvant
aspirin treatment in PIK3CA mutated
colon cancer patients
Prof. Dr. med. Ulrich Güller, MD, MHS, FEBS
PD Dr. med. et phil. Markus Jörger, MD, PhD
SAKK 41/13: PIK3CA-Mutations Aspirin Colon Cancer
Rationale
• Aspirin inhibits cyclo-oxygenase-2
• Inhibition of cyclo-oxygenase-2 results in
down-regulation phosphatidylinositol 3-kinase
(PI3K) signaling activity
Güller/Horber
SAKK 41/13: PIK3CA-Mutations Aspirin Colon Cancer
Güller/Horber
SAKK 41/13: PIK3CA-Mutations Aspirin Colon Cancer
Background
• Retrospective analysis
• Data from the Nurses` Health Study and the
Health Professionals Follow-up Study
• 964 patients with colorectal cancer
• 17% PIK3 mutations
• Data containing aspirin use (325mg/day) and
PIK3CA mutation
Güller/Horber
SAKK 41/13: PIK3CA-Mutations Aspirin Colon Cancer
Cancer-Specific Survival
Güller/Horber
SAKK 41/13: PIK3CA-Mutations Aspirin Colon Cancer
Overall Survival
Güller/Horber
SAKK 41/13: PIK3CA-Mutations Aspirin Colon Cancer
Study Proposal: Inclusion Criteria
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Patients aged 18 – 85 years
Histologically proven colon adenocarcinoma
Complete (R0) Resection
Stage II and III
Life expectancy > 3 years
Willing to consent
No medical conditions requiring aspirin or NSAIDS
No upper GI-bleeding within the past 12 months
• PIK3CA mutation
Güller/Horber
SAKK 41/13: PIK3CA-Mutations Aspirin Colon Cancer
Study Proposal
Potentially eligible colon cancer patients
PIK3CA testing
PIK3CA mutated patients
2:1 Randomization
Aspirin 300mg daily/
Standard Chemo if indicated
Follow-up
Placebo daily/
Standard Chemo if indicated
Follow-up
SAKK 41/13: PIK3CA-Mutations Aspirin Colon Cancer
Critical Issues
• Large number needed to screen (n= 1088)
• Funding
Strengths
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Relevant public health problem
Feasibility: Simple intervention
Novelty
Enthusisam in Medical Oncology Community
SAKK 41/13: PIK3CA-Mutations Aspirin Colon Cancer
Acknowledgements
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Dr. med. et sc. D. Horber
Dr. phil. Ch. Pilop, Head Trial Coordinator SAKK
Dr. phil. Stefanie Hayoz, SAKK Statistician
Mr. Severin Strasky, Funding Specialist SAKK
Prof. Dr. med. A. Roth
Prof. Dr. W. Jochum
Prof. B. Thürlimann, President SAKK
Dr. med. M. Montemurro, President SAKK GI Group
Prof. Th. Cerny
Güller/Horber