The cetuximab experience: developing predictive biomarkers in oncology.

The anti-EGF receptor monoclonal antibody cetuximab provides a case study for the development of predictive biomarkers in oncology. The identification and validation of KRAS mutation status as a predictor of lack of benefit from cetuximab in metastatic colorectal cancer provides an important first step. However, KRAS mutation status does not appear to be predictive of cetuximab benefit in advanced non-small-cell lung cancer, illustrating the necessity for separate biomarker validation to occur across tumor types. Numerous candidate biomarkers have been suggested based on noncontrolled exploratory analyses, but they require validation in sufficiently sized controlled studies. Key pending issues include distinguishing markers predictive of treatment benefit from those prognostic of disease outcome, selecting the best specimen for analysis (determining the tissue type and collection site, as well as the sample matrix type); and optimizing and standardizing assay technology and scoring systems, particularly for markers expressed over a continuous dynamic range.