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Invited Commentary
April 2017

The KRAS Variant as a Predictive Biomarker of Cetuximab Response in Head and Neck Cancer

Author Affiliations
  • 1Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
  • 2Division of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
  • 3Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
  • 4Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
 

Copyright 2016 American Medical Association. All Rights Reserved.

JAMA Oncol. 2017;3(4):491-492. doi:10.1001/jamaoncol.2016.5686

In their interesting report, Weidhaas et al1 posit that a germline mutation in the 3′ untranslated region of the KRAS variant is a predictive marker of improved response to cetuximab for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). While the results presented therein are intriguing, we would advise caution regarding their interpretation. The study by Weidhaas et al has several strengths; first, being focused on a well-characterized germline polymorphism that has been previously described as a predictive biomarker in a similar context for colon cancer.2 The evaluation of a single marker increases statistical power by limiting the number of comparisons performed3; however, while only 1 variant was analyzed, multiple hypotheses were evaluated, thereby increasing the potential for inflated type I error.3

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