1. Raymond N. DuBois, M.D., Ph.D. Executive Director
Biomarkers for Colorectal Cancer
The National Biomarker Development Alliance
Forum
March 25, 2013
Raymond N. DuBois, M.D., Ph.D.
Executive Director

2. The Problem
Worldwide about 1 million people develop colorectal cancer each year. Of these, 50% will die of systemic disease within 5 years of their diagnosis.

3. 50
150
250
350
450
30- 34
35- 39
40- 44
45- 49
Age
75- 79
70- 74
65- 69
60- 64
80- 84
85+
55- 59
50- 54
Incidence
Per/100,000
Normal Epithelium
Small Adenoma
Large Adenoma
Cancer
Metastatic spread
APC/Wnt
-catenin
Kras
BRaf
Smad4
TGFRII
PI3K/
PTEN
p53/
Bax

4. Biomarkers for detection of CRC

5. Impact of KRAS mutations on patients treated with an EGFR antagonist
Treatment response rate
Median patient survival
Therapy
KRAS mutation
positive
KRAS mutation
negative
KRAS mutation
positive
KRAS mutation
negative
Metastatic CRC
Cetuximab
0/36 = 0% 34/78 = 44% weeks (PFS) weeks (PFS)
Panitumumab
0/84 = 0% /124 = 17% weeks (PFS) weeks (PFS)

6. Using biomarkers wisely has the potential to save health care dollars
Assume there are ∼50,000 people per year with metastatic CRC in the USA.
The estimated cost savings per patient in the cetuximab-only strategy is $8,040.
Using KRAS testing to direct therapeutic decisions would save over $400 million per year
Overview of the most important pathways that can be targeted in KRAS mutant CRC.