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Optimizing EGFR targeted treatment in metastatic colorectal cancer

October 31, 2008

Analysis of:Targeting EGFR in Colorectal Cancer | content.nejm.org

The identification of reliable biomarkers predicting EGFR- targeted therapy outcomes presents a major challenge in the treatment of colorectal cancer ( CRC). Determination of EGFR levels, currently used, are a poor predictor of response to cetuximab therapy.EGFR protein expression, gene amplification and mutation have little predictive value in colorectal cancer. KRAS mutations are present in over 30% of CRC and were shown to confer resistance to anti-EGFR monoclonal antibodies. Karapetis et al analyzed tumors obtained in a randomized, phase 3, study evaluating the effect of cetuximab versus best supportive care on survival among patients with metastatic CRC.Tumor material was analyzed as to the mutation status of KRAS gene.KRAS mutations were associated with poor response to therapy, shorter progression- free and overall survival in patients with CRC treated with cetuximab.These results indicate the clinical relevance of KRAS mutations confirming earlier retrospective studies.

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