Epidermal growth factor receptor-negative colorectal cancer: is there truly such an entity?
The epidermal growth factor receptor (EGFR) has been identified as a targer for anticancer therapies. Cetuximab is a chimeric murin-human monoclonal antibody that targets the extracellular domain of the EGFR. Based on the (un proven) assumption that the presence of this receptor would quantitatively correlate with activity of cetuximab, early clinical trials with cetuximab required demonstration of the receptor by immunohistochemical (IHC) techniques. However, assumptions were made regarding the stability of EGFR expression and the reproducibility of this IHC expression that , in retrospect, were almost certainly unrealistic and are incorrect. Current techniques lack the sensitivity and predictability to inform decisions as to the usefulness of cetuximab or other anti-EGFR therapies in the treatment of colorectal or other cancers. As such, the IHC staining for EGFR that is currently in use lacks any meaningful clinical predictive value and has no use in the management of patients with cancer. Current data do not support the use of the EGFR IHC stain for making any clinical decisions regarding patient management. No patient should be refused treatment with an EGFR-targeting agent solely on the basis of a negative EGFR IHC test and no patient should be given anti-EGFR therapy simply on the basis of a positive or strongly positive EGFR test result.
Saltz
Leonard
L
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. saltzl@mskcc.org
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000032:analysis; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000503:physiopathology*; D003657:Decision Making; D066246:ErbB Receptors / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005188:False Negative Reactions; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D018579:Patient Selection; D011379:Prognosis; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D000068818:Cetuximab