Panitumumab: Human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer

Abstract

Panitumumab, formerly known as ABX-EGF, was the first recombinant human immunoglobulin G2 monoclonal antibody approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing metastatic colorectal cancer (mCRC) refractory to fluoropyrimidine-, oxaliplatin-, and/or irinotecan-containing chemotherapeutic regimens. The purpose of this review was to evaluate the pharmacokinetic and pharmacodynamic properties, clinical efficacy, and safety profile of panitumumab in the treatment of metastatic colorectal cancer. Computerized searches of MEDLINE and International Pharmaceutical Abstracts from 1985 to August 15, 2007, were performed with the search terms panitumumab, ABX-EGF, EGFr, and colorectal cancer. All available clinical trials and ongoing trials were included in this review. Relevant abstracts presented at the annual meetings of the American Society of Clinical Oncology, American Association for Cancer Research, and Gastrointestinal Cancer Symposium (1999-2007) also were reviewed and included. Preclinical and clinical studies have established a role for panitumumab in mCRC refractory to multiple chemotherapeutic regimens. In a Phase III trial of panitumumab plus best supportive care (BSC) versus BSC alone in patients with refractory mCRC, panitumumab was found to have efficacy in time-related end points, such as progression-free survival. In the panitumumab group, a significant (46%) reduction in tumor progression rate was reported compared with BSC (hazard ratio, 0.54; 95% CI, 0.44-0.66; P < 0.001). At the present time, the use of panitumumab as first-line treatment for mCRC with standard chemotherapy and bevacizumab is not indicated due to increased toxicity with no advantage in efficacy. The efficacy of panitumumab is being evaluated in other solid tumors, such as lung, breast, ovarian, bladder, and head and neck cancers. Panitumumab appears to have relatively acceptable tolerability and is now available as an additional option for patients with mCRC refractory to multiple chemotherapeutic regimens.