Nintedanib: examining the development and mechanism of action of a novel triple angiokinase inhibitor.

Antiangiogenic agents are effective standard-of-care options in several malignancies, but are generally associated with only modest improvements in survival, as well as leading to additional toxicities. Furthermore, almost all patients develop acquired resistance to therapy, possibly due to the activation of alternative proangiogenic pathways. Here we discuss: the rationale for developing nintedanib, an agent that simultaneously inhibits signaling pathways activated by platelet-derived growth factor, FGF, as well as VEGF; how its distinctive inhibitory and pharmacokinetic profile could underlie promising efficacy and tolerability observed in Phase II trials in patients with relapsed/refractory non-small cell lung cancer, advanced ovarian cancer and metastatic colorectal cancer; the ongoing Phase III program that is assessing nintedanib in these areas of major unmet medical need; and recent progress in the development of biomarkers that may predict response to nintedanib.