Abstract
Two anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) have been approved in Canada for the treatment of metastatic colorectal cancer (mCRC) - cetuximab, a mouse-human chimeric MoAb, and panitumumab, a fully human MoAb. This paper reviews the efficacy of the anti-EGFR monoclonal antibodies cetuximab and panitumumab - both as monotherapy and in combination with cytotoxic chemotherapy - in the treatment of mCRC. Both cetuximab and panitumumab have demonstrated clinical efficacy in monotherapy in patients with mCRC, an advantage that has recently been found to be limited largely to those with wild-type KRAS tumors. Advantages of using these agents in monotherapy include reduced cost and toxicity. While the addition of cetuximab to irinotecan has shown superior progression-free survival and response compared with cetuximab monotherapy, there is currently no evidence for a benefit of panitumumab in combination with irinotecan.
Highlights
There are an estimated 22,000 new cases of colorectal cancer (CRC) each year in Canada
When administered in combination with FOLFOX, panitumumab significantly prolonged progression-free survival (PFS) compared with FOLFOX alone (9.6 months vs. 8.0 months; HR = 0.80; 95% CI 0.66–0.97; p = 0.0234) in the first-line treatment of patients with KRAS wild-type metastatic CRC (mCRC)
Preliminary results from a two-part, phase I study of patients with epidermal growth factor receptor (EGFR)-expressing mCRC who had not received previous chemotherapy demonstrated that the pharmacokinetics of cetuximab were comparable between a weekly 250 mg/m2 regimen and a regimen of cetuximab 500 mg/m2 given every two weeks[63]
Summary
There are an estimated 22,000 new cases of colorectal cancer (CRC) each year in Canada. When diagnosed in the early stages of disease, CRC is associated with a five-year survival rate of up to 90%2. For those with metastatic CRC (mCRC), which represents approximately 20% of first diagnoses, the five-year survival rate is only 10%2,3. As most patients eventually develop resistance to these therapies, new active treatment options in this setting were needed. Insights into the molecular pathogenesis of CRC prompted the development of specific target-directed therapies for the treatment of mCRC, including monoclonal antibodies (MoAbs) that target the epidermal growth factor receptor (EGFR). The two anti-EGFR MoAbs approved in Canada for the treatment of mCRC are cetuximab, a mouse-human chimeric MoAb, and panitumumab, a fully human MoAb
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