Germline Mutation Predicts Response To Cetuximab in Colon Cancer Interview with:

Dr. Geoffrey Liu, MD MSC Princess Margaret Hospital/Ontario Cancer Institute University of Toronto Toronto, Ontario Canada

Dr. Geoffrey Liu

Dr. Geoffrey Liu, MD MSC
Princess Margaret Hospital/Ontario Cancer Institute
University of Toronto
Toronto, Ontario
Canada What is the background for this study? What are the main findings?

Dr. Liu: Cetuximab is a monoclonal antibody therapy used in metastatic colorectal cancer patients when other chemotherapy options have been exhausted. Currently, the only useful biomarker to determine whether metastatic colorectal cancer patients will benefit from the drug, cetuximab, is whether patients carry a RAS mutation in their tumours. We evaluated additional biomarkers using samples from a Phase III clinical trial led by the Canadian Cancer Trials Group and the Australasian Gastrointestinal Trials Group. Our study identified a germline, heritable biomarker, a FCGR2A polymorphism, that further identifies an additional subgroup of patients who would benefit most from receiving cetuximab. This is important because the drug does have toxicity and is expensive to use; patients who are found not to likely benefit from this drug can go on quickly to try other agents, including participation in clinical trials. What should readers take away from your report?

Dr. Liu: We anticipate that a number of these markers will be identified and carefully studied over time, such that a panel of such biomarkers will eventually inform the way we select drugs for individual patients. Right now, these findings are exciting but do require additional validation and prospective testing before it can be used in the clinical setting. What recommendations do you have for future research as a result of this study?

Dr. Liu: We are in the process of validating these results in additional randomized clinical trials. Thank you for your contribution to the community.


Fc-γ Receptor Polymorphisms, Cetuximab Therapy, and Survival in the NCIC CTG CO.17 Trial of Colorectal Cancer

Geoffrey Liu, Dongsheng Tu, Marcia Lewis, Dangxiao Cheng, Leslie A. Sullivan, Zhuo Chen, Eric Morgen, John Simes, Timothy J. Price, Niall C. Tebbutt,Jeremy D. Shapiro, G. Mark Jeffery,

Daniel Mellor, Thomas Mikeska, Shakeel Virk, Lois E. Shepherd, Derek J. Jonker, Christopher J. O’Callaghan,John R. Zalcberg, Christos S. Karapetis, and Alexander Dobrovic

Clin Cancer Res May 15, 2016 22:2435-2444; doi:10.1158/1078-0432.CCR-15-0414

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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