Epidermal Growth Factor Receptor (EGFR) is a member of the HER/ERB family of receptor kinases and represents an important therapeutic target in the management of advanced and metastatic colorectal cancer (CRC). Cetuximab was the first anti-EGFR monoclonal antibody to be approved for metastatic CRC, with modest clinical activity in first, second and third line, singly and in combination.

Oncogenic activation of pathways downstream of EGFR involves a well-defined cascade that engages a variety of signaling proteins, including KRAS, RAF and PI3K and retrospective analysis,  demonstrated that mutant  KRAS was found to be an important predictive biomarker for poor response to cetuximab and panitumumab. Selection of patients with wild type RAS (extending the mutational screen to cover N RAS and additional KRAS exons) show significantly greater benefits than the unstratified, general patient population, leading to changes in the labelled use of these drugs. International guidelines leave open; the optimal combination chemotherapy for use with these antibodies; timing, whether first, second or even third line; utility in patients who are candidates for resection of metastases.

Somewhat surprisingly, these EGFR inhibitors have no role to play in the adjuvant therapy of early stage CRC. Nevertheless, they have an undoubted role in the management of advanced CRC and future research efforts may focus further on developing positive markers of activity in patients with KRAS wild type tumours.