lenvatinib

Research Excerpts

Overview

Lenvatinib is an oral multikinase inhibitor that selectively inhibits vascular endothelial growth factor (VEGF) receptors 1 to 3 and other proangiogenic and oncogenic pathway-related receptor tyrosine kinases. It is a multi-kinase inhibitor for widely treating thyroid cancer.

Effects

Luvatinib has been approved as a first-line systemic treatment for advanced HCC. It is the first agent to achieve non-inferiority against sorafenib. Lenvatinib shows promising efficacy in targeted therapies to treat anaplastic thyroid carcinoma.

Actions

Lenvatinib may suppress tumor formation by inhibiting angiogenesis, and via an additional direct antiproliferative effect in some liver cancer cells. It may also suppress NF-κB translocation and activation.

Treatment

Lenvatinib treatment activated the platelet-derived growth factor receptor-extracellular regulated protein kinase (PDGFR-ERK) pathway in HCC. The drug was the only significant predictor of better OS and time to tumor progression.

Toxicity

No head-to-head postmarket surveillance study has compared the differences in adverse events (AEs) between axitinib (AXI) + pembrolizumab (PEMBRO) and lenvatinib (LEN) plus PEM BRO. The most common adverse events of len vatinib were hypertension, proteinuria, diarrhea, appetite decrease, w.

Pharmacokinetics

There were sex differences in the pharmacokinetic characteristics of lenvatinib. There was little change in the terminal elimination phase half-life of midazolam when administered with lenvATinib. As lenvatinib becomes more widely available, a better understanding of its effects will be possible.

Compound-Compound Interactions

Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents. Previous studies found that transarterial chemoembolization (TACE) combined with lenvatinib had also shown efficacy in the unresectable HCC.

Bioavailability

The relative bioavailability of lenvatinib in capsule form was 90% vs. 90% in all the species tested. Total clearance and volume of distribution were relatively low.

Dosage Studied

The dosing and adverse-event management strategies for lenvatinib have been developed through extensive clinical trial experience. A population pharmacokinetic model was established, which can be used to simulate clinical trials or various dosing scenarios.