Integration of panitumumab into the treatment of colorectal cancer

Conventional chemotherapy increases progression-free survival (PFS) and overall survival (OS) of metastatic colorectal cancer (mCRC) patients versus best supportive care (BSC). However, the efficacy of chemotherapy is limited. Recently approved monoclonal antibodies (MoAb) have a different mechanism of action, targeting growth factors or their receptors. Panitumumab is a fully human IgG2 MoAb directed against the epidermal growth factor receptor (EGFR). In phase II trials, panitumumab showed preliminary activity in chemorefractory mCRC. This efficacy was confirmed in a randomized pivotal phase III trial, which compared single-agent panitumumab plus BSC versus BSC alone. Several ongoing clinical trials are evaluating panitumumab in combination with different chemotherapy regimens in first- and second-line settings. Skin toxicities, hypomagnesemia, and diarrhea are the most common adverse events associated with anti-EGFR therapy. KRAS status and skin rash have been correlated with panitumumab efficacy. This article reviews the preclinical and pharmacokinetics data, activity and tolerance of panitumumab in mCRC patients. Potential predictive factors of response are also discussed.