Lack of usefulness of epidermal growth factor receptor expression determination for cetuximab therapy in patients with colorectal cancer

Abstract

In patients with metastatic colorectal cancer, the use of cetuximab currently requires a documented tumoral epidermal growth factor receptor positivity. Responses to cetuximab, however, have been described in patients with epidermal growth factor receptor-negative tumors. We have used cetuximab in all eligible patients with metastatic colorectal cancer, whether their tumor expressed epidermal growth factor receptor or not. We assessed the cetuximab efficacy with regard to tumoral epidermal growth factor receptor expression. Twenty patients with metastatic colorectal cancer were treated off study with cetuximab and irinotecan after failure of oxaliplatin- and irinotecan-based regimens. Tumors were analyzed in all patients for epidermal growth factor receptor expression by immunohistochemistry. Tumors were positive for epidermal growth factor receptor in 12 cases and negative in eight cases. An objective response to cetuximab-based therapy was obtained in four patients (20%). Tumors of these four patients were negative for epidermal growth factor receptor expression. These results provide further evidence for the lack of usefulness of epidermal growth factor receptor detection by immunohistochemistry for cetuximab therapy in patients with metastatic colorectal cancer.

Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

“…Most studies on ovarian cancer and HER2 have evaluated the HER2 protein expression by immunohistochemistry and fluorescence in situ hybridization (FISH) with a high reported concordance between these two methods (18,19). Nevertheless, immunohistochemistry is only semi-quantitative and for HER1 there are severe difficulties in predicting response to anti-HER1 therapies by HER1 immunohistochemical testing (20)(21)(22)(23). To our knowledge, this is the first study that describes quantitative levels of all four receptors of the EGF receptor family in ovarian cancer as well as their gene expression levels.…”

Current role of antibody therapy in patients with metastatic colorectal cancer

“…Recent retrospective studies Hebbar et al, 2006) confirmed activity of CxIri or Cx alone in EGFR negative mCRC, and the practice of testing EGFR status by IHC to select for Cx (or Pa) therapy is clearly inappropriate and other predictive tests are needed (Meropol, 2005;Nygren et al, 2005;Hecht et al, 2006b). Furthermore, the expression in primary tumors does not necessarily reflect or predict the expression in metastatic sites (Scartozzi et al, 2004).…”

Correlation between efficacy and skin rash occurrence following treatment with the epidermal growth factor receptor inhibitor cetuximab: A single institution retrospective analysis

“…Likewise, NSCLC patients overexpressing EGFR have been demonstrated to have a worse outcome (14). Furthermore, current evidence suggests no association between a high EGFR cell surface expression and cetuximab response in colorectal cancer patients (15)(16)(17)(18)(19). Particularly in colorectal cancer, recent studies suggest that mutations of K-RAS gene are associated with nonresponsiveness to cetuximab, while amphiregulin and epiregulin overexpression may be markers of response (20)(21)(22)(23)(24).…”