The role of anti-epidermal growth factor receptor monoclonal antibody monotherapy in the treatment of metastatic colorectal cancer

Abstract

Despite the introduction of newer chemotherapeutic agents such as irinotecan, capecitabine and oxaliplatin, patients with metastatic colorectal cancer (mCRC) still have a poor prognosis. More effective and better-tolerated treatment strategies are needed to improve patient outcomes, particularly in subsequent lines of treatment following chemotherapy failure. The favourable efficacy and acceptable safety profiles of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) have led to the approval of panitumumab and cetuximab monotherapy for the treatment of patients with EGFR-expressing mCRC whose tumours express non-mutated (wildtype) KRAS, after failure of standard chemotherapy. Cetuximab is also approved in combination with chemotherapy for the treatment of mCRC in this patient population. In phase III monotherapy studies, panitumumab and cetuximab demonstrated significant improvements in progression-free survival when administered with best supportive care (BSC) vs. BSC alone in chemotherapy-refractory mCRC patients. A planned retrospective analysis of the panitumumab monotherapy trial was the first large-scale clinical demonstration that efficacy was confined to patients with tumours expressing wild-type KRAS. It is now recognised that anti-EGFR mAb therapy should only be used in patients whose tumours express wild-type KRAS. While generally well tolerated, anti-EGFR mAb monotherapy is associated with skin toxicity, and severity of the skin rash has been proposed as an early marker of response to treatment. BRAF, PTEN, and PI3K are also emerging as future potential predictive markers of response; however, further clinical studies are warranted to define the role of these biomarkers.