Epidermal growth factor receptor: will it ever become a therapeutic target in ovarian cancer?

Targeted therapies are increasingly being explored in the treatment of ovarian cancer. The epidermal growth factor receptor (EGFR) has received much attention as this pathway is overexpressed and/or amplified in ovarian cancer. Anti-EGFR tyrosine kinase inhibitors (TKIs) and monoclonal antibodies have been studied in combination with chemotherapy and as single agents in both the first-line and relapsed settings but unfortunately, the results have been disappointing. In this editorial, we review a recently published large randomized phase III trial conducted by Vergote et al. evaluating maintenance erlotinib in patients with ovarian, peritoneal, or fallopian tube cancer who experienced a response or stable disease (SD) after primary therapy. This study did not show a benefit to maintenance erlotinib and moreover, was not able to identify any subgroups that benefited from erlotinib. Testing for EGFR overexpression and/or amplification by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively, and mutation testing were performed on archival tumor tissue. Patients who were EGFR positive did have a worse progression-free survival (PFS) and overall survival (OS) but EGFR positivity or the presence of a mutation was not predictive of erlotinib efficacy. At this time, EGFR inhibition in ovarian cancer has not been successful and further targeting of this pathway requires an understanding of resistance mechanisms and the role of other pathways that interplay with EGFR.