For the treatment of thyroid cancer with the so called targeted therapy the angiogenesis
pathway has several potential targets. The Receptors for Vascular endothelial growth factor
(VEGF) and especially VEGFR-2 is considered to be crucial for the initiation of the formation
as well as the maintenance of tumor vasculature.
In thyroid cancer these VEGF receptors (VEGFR-1, VEGFR-2), VEGF itself and receptors of the
fibroblast growth factor (FGF) and for the platelet-derived growth factor (PDGF) are often
overexpressed. Other cells as pericytes and smooth muscle cells that are also involved in
tumor angiogenesis express these receptors as well.
Inhibitors of the VEGFR or PDGFR pathway have been tested in thyroid cancer with positive
results. However there is no treatment that is generally considered as standard of care for
patients with differentiated thyroid cancer (DTC) or medullar thyroid cancer (MTC) who have
progressed on one line of therapy. The classical cytotoxic chemotherapy has not shown a
clinically meaningful benefit yet.
Nintedanib is a triple angiogenesis inhibitor which inhibits receptors of VEGF, FGF and PDGF.
Therefore it might act not only on endothelial cells but also on pericytes and smooth muscle
cells. Nintedanib also interacts with other kinases such as RET. Because of this multi-kinase
activity rationale exists to investigate the effect in MTC and DTC.
Because it targets these three major angiogenesis signaling pathways it might prevent further
tumor growth and related tumor escape mechanisms. Therefore nintedanib may be active in
patients who have progressed on agents that target only one pathway.
Phase:
Phase 2
Details
Lead Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC