What could Nintedanib (BIBF 1120), a triple inhibitor of VEGFR, PDGFR, and FGFR, add to the current treatment options for patients with metastatic colorectal cancer?

Abstract

Increasing knowledge of the pro-angiogenic processes involved in the progression of metastatic colorectal cancer (mCRC) has resulted in the clinical development of several anti-angiogenic agents, with bevacizumab currently being the only approved agent for mCRC. Nintedanib (BIBF 1120) has been shown to block the vascular endothelial growth factor receptor (VEGFR), the platelet-derived growth factor receptor (PDGFR), and the fibroblast growth factor receptor (FGFR). By targeting FGFR signaling, nintedanib may overcome resistance to previous anti-VEGF treatments, and may represent a better approach in patients with high basal levels of circulating FGFs. In this article, the angiogenic mechanisms implicated in mCRC are reviewed (focusing on the signaling pathways activated by VEGFR, PDGFR, and FGFR), along with the clinical data for nintedanib in the context of other anti-angiogenic tyrosine kinase inhibitors under clinical development for mCRC. Biomarkers that could predict response to nintedanib are also discussed.