New Preclinical Data Show Combination of Lenvatinib and Everolimus Yield Greater Antitumor Activity Than Either Agent Alone in Kidney Cancer

HATFIELD, England, April 19, 2016 /PRNewswire/ --


Data from the American Association for Cancer Research annual meeting support significant combination effects and possible mechanisms of action

of lenvatinib plus everolimus  

A preclinical study of lenvatinib plus everolimus[1] demonstrates enhanced inhibition of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF)-induced angiogenesis than for either agent alone in human endothelial cell models. The combination also showed synergistic enhancement against bFGF- driven angiogenesis, distinguishing this from other VEGFR2 tyrosine kinase inhibitors (TKIs). These data are one of a number of lenvatinib abstracts presented this week at the American Association for Cancer Research (AACR) Annual Meeting 2016, New Orleans, USA.

"Lenvatinib and everolimus appear to be working together to produce significant combination effects, including synergistic antiangiogenic and additive antiproliferative activities against human umbilical vein endothelial cells (HUVEC). This is because the agents together simultaneously inhibit VEGFR-TK/FGFR-TK and mammalian target of rapamycin (mTOR). In preclinical models, this study examined the inhibition of molecular drivers of cancer associated with development of new blood vessels that tumours need for growth and drivers of rapid growth of cancer cells. The study revealed a possible mechanistic basis of the combination of these two drugs, which could explain the observed magnified clinical benefit," comments Dr Takashi Owa, Chief Medicine Creation Officer Oncology Business Group, Corporate Officer Eisai Co., Ltd.

Lenvatinib is indicated for the treatment of adult patients with progressive locally advanced or metastatic, differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI).[2] Lenvatinib is an oral multiple receptor tyrosine kinase (RTK) inhibitor that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors in addition to other proangiogenic and oncogenic pathway-related RTKs including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet-derived growth factor (PDGF) receptor PDGFRalpha; KIT; and rearranged during transfection (RET) proto-oncogene.

A recent Phase II study found lenvatinib in combination with everolimus significantly extends progression-free survival in unresectable advanced renal cell carcinoma (RCC), when compared to either treatment alone.[3] People treated with the combination regimen experience a median progression-free survival of 14.6 months compared with 5.5 months for those who receive everolimus alone (HR 0.40; 95% CI: 0.24-0.68; p

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