Lenvatinib enhances antitumor immunity of anti-PD-1 antibody.

Abstract

Lenvatinib is an orally available multi-tyrosine kinase inhibitor that mainly targets vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling. These inhibitory activities of lenvatinib exhibit antitumor efficacy, mainly due to their repressive effects on angiogenesis. In addition, a recent non-clinical evaluation using mouse tumor models revealed that lenvatinib causes immunomodulatory effects, including activation of effector T-cells and regulation of tumor-associated macrophages (TAMs). Combined treatment with lenvatinib and anti-programmed cell death-1 antibody (anti-PD-1) resulted in enhanced antitumor activity relative to monotreatment with anti-PD-1 or lenvatinib. This review summarizes the antitumor mechanisms of lenvatinib and of lenvatinib plus anti-PD-1 combination therapy.