Expression of the epidermal growth factor receptor (EGFR or HER1) and human epidermal growth factor receptor 2 (HER2) in a large scale metastatic colorectal cancer (mCRC) trial

Abstract

3630 Background: EGFR is commonly expressed in CRC (72–82%) and is therefore a target for anticancer therapies, such as the anti-EGFR monoclonal antibody cetuximab (Erbitux). There appears to be no correlation between tumor response to cetuximab and EGFR expression level. This may be due in part to co-expression of other ErbB receptors, such as HER2. The current results describe EGFR and/or HER2 expression in a population of CRC patients. Methods: In this large multi-center phase II study, patients with EGFR-expressing mCRC, who progressed on irinotecan-based treatment, receive cetuximab plus irinotecan. Immunohistochemistry on paraffin-embedded tumor material, obtained before recruitment into the trial, was used to assess EGFR and HER2 expression (defined as receptor membrane staining in > 0% of evaluated tumor cells). Results: Of 1206 tumor samples assessed for EGFR, 1034 (86%) were EGFR-expressing. Of a subgroup of 451 tumor samples tested for HER2, 292 (65%) were HER2-expressing: 253 (56%) expressed both EGFR and HER2, 120 (27%) expressed EGFR but not HER2, 39 (9%) expressed HER2 but EGFR was undetectable, and in 39 (9%) neither receptor was detectable. For all four subgroups, demographic and disease characteristics were similar, except that there were more rectal tumors in the EGFR-undetectable population (44% EGFR-undetectable vs. 30% EGFR-expressing). Conclusions: More than half of the CRC tumor samples assessed expressed both EGFR and HER2. HER2 expression was more common in the EGFR-expressing population compared with the EGFR-undetectable population. Evaluation of EGFR/HER2 co-expression as a potential predictor of the 12-week efficacy result will be presented.