EGFR expression using immunohistochemistry (IHC) testing as a tool for selecting patients (pts) for treatment with cetuximab

13000 Background: EGFR expression, as determined by IHC, is currently used to select patients for cetuximab therapy. Based on prior studies in colorectal cancer patients, approximately 60 to 75% of patients express EGFR. There is increasing evidence that EGFR expression is not predictive of response to cetuximab therapy, and does not properly select patients who might benefit from such therapy (Chung et al 2005, Saltz et al 2005, Scartozi et al 2004, NCCN 2005). Such selection limits access to a considerable number of patients who might otherwise benefit. Methods: A clinical trial of cetuximab (Erbitux®) monotherapy is being conducted in 60 EGFR-undetectable patients with metastatic colorectal cancer at 14 sites in the US and Canada to explore the relationship between EGFR expression and cetuximab activity. Results: As of January 5, 2006, 112 patients have been screened. Of these patients, 33 (29%) were EGFR-undetectable and continued screening for study enrollment; 52 (46%) tested positive for EGFR expression; and 2 (2%) did not have enough tissue to evaluate EGFR status and were not enrolled onto the trial. The remaining 25 pts (22%), were initially found to be EGFR-undetectable by IHC testing at local labs, but were subsequently identified as EGFR-positive after reevaluation at a highly experienced, centralized laboratory. Conclusion: The majority of patients tested for EGFR expression are tested using the EGFR pharmDx™ IHC assay. Results of the IHC-based assay for EGFR expression are highly dependent upon sample preparation and the methods used in conducting the assay. Variability in methods among labs may result in poor identification of pts expressing EGFR. This finding, together with the growing evidence that EGFR expression is not predictive of response to cetuximab therapy, indicate that the current routine practice of tumor IHC EGFR testing for the purpose of selecting cetuximab therapy may be inappropriate and pts who could potentially benefit from cetuximab therapy are being excluded from a treatment option. [Table: see text]