Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies

• Published in: Expert review of anticancer therapy Vol. 22; no. 4; pp. 383 - 400
• Main Authors: Motzer, Robert J., Taylor, Matthew H., Evans, Thomas R. Jeffry, Okusaka, Takuji, Glen, Hilary, Lubiniecki, Gregory M., Dutcus, Corina, Smith, Alan D., Okpara, Chinyere E., Hussein, Ziad, Hayato, Seiichi, Tamai, Toshiyuki, Makker, Vicky
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.04.2022
• Subjects: Antineoplastic Agents - adverse effects; Carcinoma, Renal Cell - pathology; Dosing; endometrial carcinoma; hepatocellular carcinoma; Humans; Iodine Radioisotopes; Kidney Neoplasms - drug therapy; lenvatinib; Liver Neoplasms - drug therapy; pembrolizumab; Phenylurea Compounds - adverse effects; Protein Kinase Inhibitors - adverse effects; Quinolines - adverse effects; renal cell carcinoma; safety; thyroid carcinoma; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - pathology; TKI; Dosing; pembrolizumab; renal cell carcinoma; thyroid carcinoma; TKI; lenvatinib; safety; endometrial carcinoma; hepatocellular carcinoma
• ISSN: 1473-7140; 1744-8328
• DOI: 10.1080/14737140.2022.2039123

Lenvatinib is an oral multitargeted tyrosine kinase inhibitor that has shown efficacy and manageable safety across multiple cancer types. The recommended starting doses for lenvatinib differ across cancer types and indications based on whether it is used as monotherapy or as combination therapy. This review covers clinical trials that established the dosing paradigm and efficacy of lenvatinib and defined its adverse-event profile as a monotherapy; or in combination with the mTOR inhibitor, everolimus; or the anti-PD-1 antibody, pembrolizumab; and/or chemotherapy. Lenvatinib has been established as standard-of-care either as a monotherapy or in combination with other anticancer agents for the treatment of radioiodine-refractory differentiated thyroid carcinoma, hepatocellular carcinoma, renal cell carcinoma, and endometrial carcinoma, and is being investigated further across several other tumor types. The dosing and adverse-event management strategies for lenvatinib have been developed through extensive clinical trial experience. Collectively, the data provide the rationale to start lenvatinib at the recommended doses and then interrupt or dose reduce as necessary to achieve required dose intensity for maximized patient benefit. The adverse-event profile of lenvatinib is consistent with that of other tyrosine kinase inhibitors, and clinicians are encouraged to review and adopt relevant symptom-management strategies.