Targeted therapy in advanced colorectal cancer: more data, more questions

Colorectal cancer (CRC) remains the third most common malignancy and the third leading cause of cancer death worldwide. The introduction of new chemotherapeutics and monoclonal antibodies into the treatment protocols for advanced CRC has significantly improved the outcomes. Nowadays, oncologists have a wide range of agents to choose for the treatment of advanced CRC; however, their optimal administration remains unclear. This article presents recently published data from the trials evaluating the use of monoclonal antibodies in advanced CRC with a particular emphasis on the predictive and prognostic factors of response to targeted therapy. The results from the CRYSTAL and OPUS studies indicate that the benefit from the addition of cetuximab to first-line chemotherapy is restricted to patients with the wild-type KRAS gene, with the best outcomes observed among those with unmutated forms of both the KRAS and BRAF genes. However, that has not been confirmed in the preliminary data from the COIN trial. Panitumumab has been shown to improve the outcomes when combined with first-line and second-line chemotherapy, but again mostly in patients with wild-type KRAS. The article also describes the detrimental effect of combined anti-vascular endothelial growth factor and anti-epidermal growth factor blockade in the first-line setting observed in the PACCE and the CAIRO-2 trials. Finally, results from the BRiTE registry indicating benefit from continuation of bevacizumab after progression on the first-line regimen are discussed in the context of maintenance therapy. Modern treatment for advanced CRC is based not only on clinical and anatomo-pathological but also molecular tumour characteristics. Our knowledge of the optimal administration of monoclonal antibodies in advanced CRC has extended significantly over the last few years; however, there are still many questions that have to be answered in future trials.