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?

Jaume Capdevila; Alfredo Carrato; Josep Tabernero; Enrique Grande

doi:10.1016/j.critrevonc.2014.05.004

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?

Crit Rev Oncol Hematol. 2014 Nov;92(2):83-106. doi: 10.1016/j.critrevonc.2014.05.004. Epub 2014 May 14.

Authors

Jaume Capdevila¹, Alfredo Carrato², Josep Tabernero³, Enrique Grande²

Affiliations

¹ Medical oncology Department, Hospital Vall d'Hebrón, Barcelona, Spain. Electronic address: [email protected].
² Medical oncology Department, Hospital Ramón y Cajal, Madrid, Spain.
³ Medical oncology Department, Hospital Vall d'Hebrón, Barcelona, Spain.

PMID: 24924525
DOI: 10.1016/j.critrevonc.2014.05.004

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.

Keywords: Angiogenesis; Metastatic colorectal cancer; Nintedanib; VEGFR.

Publication types

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

MeSH terms

Antineoplastic Agents / therapeutic use*
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / secondary*
Humans
Indoles / therapeutic use*
Receptors, Fibroblast Growth Factor / antagonists & inhibitors*
Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors*
Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
Signal Transduction / drug effects*

Substances

Antineoplastic Agents
Indoles
Receptors, Fibroblast Growth Factor
Receptors, Platelet-Derived Growth Factor
Receptors, Vascular Endothelial Growth Factor
nintedanib