Raymond N. DuBois, M.D., Ph.D.Raymond N. DuBois, M.D., Ph.D.
Executive DirectorExecutive Director
The National Biomarker Development AllianceThe National Biomarker Development AllianceForumForum
March 25, 2013 March 25, 2013
Biomarkers for Colorectal Cancer
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.
5050
150150
250250
350350
450450
30-30-343435-35-393940-40-444445-45-4949
AgeAge
75-75-7979
70-70-7474
65-65-6969
60-60-6464
80-80-848485+85+55-55-
595950-50-5454
IncidenceIncidencePer/100,000Per/100,000
Normal Normal EpitheliumEpithelium
Small Adenoma
Large Adenoma CancerCancer
Metastatic spread
APC/WntAPC/Wnt-catenin-catenin
KrasKrasBRafBRaf
Smad4Smad4TGFTGFRIIRII
PI3K/PI3K/PTENPTEN
p53/p53/BaxBax
TherapyTreatment response rate Median patient survival
Metastatic CRC
Impact of KRAS mutations on patients treated Impact of KRAS mutations on patients treated with an EGFR antagonist with an EGFR antagonist
Cetuximab
KRAS mutation positive
KRAS mutationnegative
KRAS mutation positive
KRAS mutationnegative
Panitumumab
0/36 = 0% 34/78 = 44% 9 weeks (PFS) 32 weeks (PFS)
0/84 = 0% 21/124 = 17% 7 weeks (PFS) 12 weeks (PFS)
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