TARGETING TREATMENT FOR COLORECTAL CANCER: THE EGFR ANTIBODY STORY

Frequent overexpression of the epidermal growth factor receptor in colorectal cancer was the rationale for the development of anti-epidermal growth factor receptor antibodies. The development of the drug cetuximab, led to considerable expectations in terms of clinical and commercial success. The registration of the anti-epidermal growth factor receptor antibodies, cetuximab and panitumumab, was granted on the basis of improvement in progression free survival. Other drugs targeting the epidermal growth factor receptor, such as the oral tyrosine kinase inhibitors, have minimal efficacy in colorectal cancer when used alone, and are too toxic when combined with chemotherapy. Cetuximab and panitumumab have activity only in patients with metastatic disease who have a reasonable performance status. Retrospective analyses of tumour samples collected from trial enrolees showed the presence of KRAS mutations in exon 2 were a negative predictor of response to the anti-EGFR antibodies. Recent data suggests that patient selection should be based on a more extensive analysis of KRAS, NRAS, BRAF and potentially other genes. The anti-EGFR antibodies have been used alone or in combination with other chemotherapies, however use with oxaliplatin appears to compromise patient outcomes. When used as monotherapy, toxicities include rash and fatigue, however more severe adverse effects are observed when used with chemotherapy. Anti-epidermal growth factor receptor treatments for colorectal cancer demonstrate the complexity of using targeted treatments. They remain a useful treatment in colorectal cancer, but have not fulfilled their initial expectation of being highly effective and non-toxic treatments.