Panitumumab: in metastatic colorectal cancer with wild-type KRAS

Abstract

Panitumumab is a fully human IgG2 monoclonal antibody that is highly selective for the epidermal growth factor receptor (EGFR), which is overexpressed in 25-77% of colorectal cancers and is often associated with a poor prognosis. Binding of panitumumab to EGFR reduces cell proliferation and mediator production, and induces apoptosis. In a comparative, phase III trial in adult patients with chemotherapy-refractory metastatic colorectal cancer, intravenous panitumumab 6 mg/kg every 2 weeks plus best supportive care (BSC) improved progression-free survival (PFS) [primary endpoint] and objective tumor response rate to a significantly greater extent than BSC alone. The improvement in PFS produced by panitumumab monotherapy was significantly greater in patients with non-mutated (wild-type) KRAS than in those with mutant KRAS (in whom no benefit from panitumumab was observed). Similarly, all patients experiencing a partial response had wild-type KRAS, while stable disease was achieved by more patients with wild-type KRAS than with mutant KRAS. The predictive value of mutant KRAS for a lack of clinical benefit with panitumumab monotherapy was supported by results from an open-label extension of the phase III study and a large phase II study. Although most patients treated with panitumumab experienced at least one adverse event, the incidence of severe adverse events resulting in discontinuation of treatment was relatively low. The most commonly reported treatment-related adverse events were skin-related toxicities, which reflect the mechanism of action of panitumumab.