Evaluation of aflibercept in the treatment of metastatic colorectal cancer

Introduction: Colorectal cancer (CRC) is currently the third most common cancer worldwide, with up to 1 million new cases diagnosed each year. Despite improvements in clinical outcomes of patients with this tumor over the past decades, prognosis remains poor with a 5-year survival rate of < 10%. The currently available systemic chemotherapeutic options for patients with colon cancer consist essentially of fluoropyrimidine-based regimens, alone or in combination with oxaliplatin or irinotecan. The addition of the anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) bevacizumab to the above mentioned first-or second-line chemotherapies has demonstrated an improvement in overall survival and a delay in disease progression. Aflibercept is a recombinant protein from the domain 2 of the VEGF receptor-2 attached to the Fc portion of IgG1. In preclinical studies, aflibercept has demonstrated a more favorable pharmacokinetic profile. Aflibercept has been evaluated in a Phase III study in combination with irinotecan-based chemotherapy in patients with metastatic CRC refractory to oxaliplatin-based chemotherapy. The results of the VELOUR study showed that the addition of aflibercept produced an advantage in both progression-free and overall survival. Areas covered: In this review article, we will look over the preclinical and clinical development of aflibercept. Expert opinion: In our opinion research is moving forward on a good path; we have seen the recent approval of aflibercept, and in the following years we might have newer standard treatment options among the latest compounds under development.