Evaluation of aflibercept in the treatment of metastatic colorectal cancer

Expert Opin Biol Ther. 2014 Oct;14(10):1493-505. doi: 10.1517/14712598.2014.947956. Epub 2014 Aug 25.

Abstract

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.

Keywords: VEGF; aflibercept; angiogenesis; colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Humans
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use*
  • Survival Rate
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor