Colon Cancer

Targets: Stage II (Recurrence Risk)
Stage III (Including Oxaliplatin Benefit)
Cetuximab (Erbitux®) Response
Development Stage: Validation (Stage II)
Early Development (Stage III)
Development (Cetuximab)
U.S. Incidence of Colon Cancer1 120,000/Year (All Stages)
Global Incidence of Colon Cancer2 1.2 Million/Year (All Stages)

About Colon Cancer and Genomic Health’s Products in Development

In the Western world, colorectal cancer (including colon cancer) is the third most common form of cancer3. Mushroom-like non-cancerous growths called polyps are often a precursor to colon cancer. Diagnosis of colon cancer is frequently made via colonoscopy, with early diagnosis often leading to a complete cure. The American Cancer Society currently recommends that almost all men and women age 50 and older undergo colon cancer screening. Current treatment for colon cancer includes surgery, followed in many cases by adjuvant chemotherapy. While the benefit of adjuvant chemotherapy has been demonstrated in stage III disease, the optimal management of stage II colon cancer remains controversial.

In April 2009, Genomic Health announced that the landmark QUASAR validation study met its primary endpoint to predict the likelihood of recurrence for stage II colon cancer patients following surgery, and that the colon cancer Recurrence Score® provided additional independent clinical value beyond standard measures of risk. Based on these positive results, Genomic Health is initiating the necessary work in its Clinical Reference Laboratory (CLIA) and proceeding with commercialization plans to make the Oncotype DX® colon cancer Recurrence Score available to physicians and patients in early 2010.

For its colon cancer program, Genomic Health and it’s collaborators, the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the Cleveland Clinic Foundation used the same rigorous clinical development strategy and standardized quantitative assay technology designed for the company's Oncotype DX breast cancer assay. More than 1,800-colon cancer patients and 760 candidate genes were evaluated in four clinical studies to select the genes for the Oncotype DX colon cancer assay. The resulting genes were then studied in more than 1,200 stage II colon cancer tumor samples from the landmark QUASAR study (Lancet 370:2020, 2007).

The development of newer targeted therapies, such as cetuximab, which targets the epidermal growth factor receptor (EGFR), offers promise for improved outcomes in resectable colon cancer but will likely further increase the complexity of treatment planning for these patients. The decision to administer adjuvant therapy (and what type of therapy to give) would be greatly aided by the availability of diagnostic tests, which would provide information on a patient’s likelihood of colon cancer recurrence and the likelihood of treatment benefit.

In May 2008, Genomic Health announced results from a study, in collaboration with Bristol-Myers Squibb (BMS) and Imclone, identifying a small number of genes that could predict response to Erbitux. These results, which need to be confirmed through additional studies, suggest that quantitative expression of a number of these identified genes used in conjunction with KRAS mutation status increases the ability to predict which patients might benefit from treatment with Erbitux over KRAS status alone.

For more information about colon cancer, visit the National Cancer Institute’s Colon Cancer page or the non-profit Colorectal Cancer Coalition.

Relevant Presentations

Stage II and Stage III Colon Cancer
2008 ASCO Gastrointestinal Cancers Symposium—Orlando, FL

Abstract # 301: Poster Presentation
Relationship Between Tumor Gene Expression and Recurrence in Patients with Stage II/III Colon Cancer Treated with Surgery + 5-FU/LV in NSABP C-06: Consistency of Results with Two Other Independent Studies
MJ O'Connell, G Yothers, S Paik, IC Lavery, JW Cowens, KM Clark-Langone, M Lopatin, JR Hackett, FL Baehner, N Wolmark

Abstract # 302: Poster Presentation
Relationship Between Tumor Gene Expression and Recurrence in an Observational Cohort of Patients with Stage II/III Colon Cancer Treated with Surgery Only: Quantitative RT-PCR Assay of 375 Genes in Fixed Paraffin-Embedded (FPE) Tissue.
I Lavery, J Hammel, J Cowens, K Clark-Langone, J Hackett, F Baehner, G Yothers, M O'Connell, N Wolmark

2006 ASCO Annual Meeting—Atlanta, GA

Abstract #3518: Poster Discussion
Relationship Between Tumor Gene Expression and Recurrence in Stage II/III Colon Cancer: Quantitative RT-PCR Assay of 757 Genes in Fixed Paraffin-Embedded (FPE) Tissue
MJ O’Connell, S Paik, G Yothers, JP Costantino, JW Cowens, KM Clark, J Baker, J Hackett, D Watson, N Wolmark

Cetuximab Response
2008 ASCO Annual Meeting—Chicago, IL

Abstract #3512: Oral Presentation
Evaluation of Tumor Gene Expression and K-Ras Mutations in FFPE Tumor Tissue as Predictors of Response to Cetuximab in Metastatic Colorectal Cancer
JB Baker, D Dutta, D Watson, T Maddala, S Shak, EK Rowinsky, L Xu, E Clark, DJ Mauro, S Khambata-Ford

  1. Mattson Jack DaVinci ©2004, 2007.
  2. Globocan 2002/ACS Cancer Facts & Figures, 2007.
  3. American Cancer Society 2007 Statistics. Available at: http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf,. Accessed July 22, 2008.