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

Biomarkers for detection of CRC

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