Lenvatinib

Lenvatinib is an oral tyrosine kinase inhibitor used in the treatment of certain advanced cancers. It is marketed under the brand name Lenvima by Eisai Co., often in collaboration with Merck & Co.. The medication works by inhibiting multiple kinase targets involved in angiogenesis and tumor proliferation, making it a multikinase inhibitor.

Medical uses

Lenvatinib is approved by the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of progressive, radioiodine-refractory differentiated thyroid cancer. It is also indicated, in combination with everolimus, for advanced renal cell carcinoma following one prior anti-angiogenic therapy. Furthermore, it is approved for first-line treatment of unresectable hepatocellular carcinoma, often in comparison to sorafenib in clinical trials like the REFLECT trial. Additional approvals include use in certain types of endometrial carcinoma in combination with pembrolizumab, an immune checkpoint inhibitor.

Adverse effects

Common adverse effects include hypertension, fatigue, diarrhea, arthralgia, myalgia, decreased appetite, weight loss, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, and abdominal pain. Serious adverse reactions can involve hepatic failure, renal failure, cardiac dysfunction, arterial thromboembolic events, hemorrhagic events, and gastrointestinal perforation. Management often requires dose interruptions or reductions, and monitoring of parameters like blood pressure and urinalysis is standard.

Pharmacology

As a multikinase inhibitor, lenvatinib potently inhibits the kinase activities of vascular endothelial growth factor receptor (VEGFR1, VEGFR2, VEGFR3), fibroblast growth factor receptor (FGFR1, FGFR2, FGFR3, FGFR4), platelet-derived growth factor receptor alpha (PDGFRα), RET, and KIT. This broad activity disrupts multiple signaling pathways critical for angiogenesis and tumor growth. The drug is administered orally and achieves peak plasma concentration within 1 to 4 hours. It is primarily metabolized by CYP3A4 enzymes in the liver and has a half-life of approximately 28 hours.

History

Lenvatinib was discovered and developed by Eisai Co. at its Tsukuba Research Laboratories. It received its first global approval in 2015 for thyroid cancer, based on the phase III SELECT trial which demonstrated significant improvement in progression-free survival. Subsequent approvals followed for renal cell carcinoma (2016) and hepatocellular carcinoma (2018). In 2019, the U.S. Food and Drug Administration granted accelerated approval for its use in advanced endometrial carcinoma. The collaboration with Merck & Co. for co-development and commercialization was expanded in 2018.

Society and culture

Lenvatinib is available under the brand name Lenvima and is on the World Health Organization's List of Essential Medicines. Its cost and access have been subjects of discussion within healthcare systems like the National Health Service in the United Kingdom. The drug has been featured in presentations at major oncology conferences such as those held by the American Society of Clinical Oncology and the European Society for Medical Oncology. Its development represents a significant area of research in targeted therapy for solid tumors. Category:Antineoplastic drugs Category:Tyrosine kinase inhibitors Category:Eisai