Raymond N. DuBois, M.D., Ph.D. Executive Director

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Presentation transcript:

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

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.

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

Biomarkers for detection of CRC

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% 9 weeks (PFS) 32 weeks (PFS) Panitumumab 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 Overview of the most important pathways that can be targeted in KRAS mutant CRC.