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

Abstract

Introduction: 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. Areas covered: 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. Expert opinion: 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.

Sustained antitumor response to lenvatinib with weekend-off and alternate-day administration in chemotherapy-refractory thymic carcinoma: a case report

“…Accumulating evidence indicates the significance of maintaining lenvatinib dose intensity to maximize patient benefit [4]. In the SELECT phase 3 trial for thyroid cancer, lenvatinib-induced tumor size reduction was prominent in the first 8 weeks of treatment, and increased lenvatinib exposure [area under the curve (AUC)] correlated with greater tumor size reduction [7].…”

“…Most patients receiving lenvatinib experience AEs, such as hypertension, proteinuria, thrombocytopenia, and fatigue, and the high incidence of AEs causing treatment interruption and dose reduction is a major obstacle in maintaining dose intensity [4]. In fact, all patients with thymic carcinoma in the REMORA trial required lenvatinib dose reduction because of severe or intolerable AEs [6].…”

“…Although the clinical impact of RDI on thymic carcinoma remains to be evaluated, these findings suggest that maintaining lenvatinib dose intensity in the early treatment phase is critical for achieving a favorable prognosis in these patients. Most patients receiving lenvatinib experience AEs, such as hypertension, proteinuria, thrombocytopenia, and fatigue, and the high incidence of AEs causing treatment interruption and dose reduction is a major obstacle in maintaining dose intensity [4]. In fact, all patients with thymic carcinoma in the REMORA trial required lenvatinib dose reduction because of severe or intolerable AEs [6].…”

Rationale Efficacy and Safety Evidence of Lenvatinib and Pembrolizumab Association in Anaplastic Thyroid Carcinoma

“…Safety results are consistent with the phase-III Study KEYNOTE-775, which evaluated lenvatinib plus pembrolizumab versus chemotherapy in patients with advanced endometrial cancer and prior treatment with platinum-based chemotherapy regimen. In this larger study, Grade 3 or higher adverse events occurred in 88.9% of the patients receiving lenvatinib plus pembrolizumab and the most frequent any-grade treatment-emergent adverse events were hypertension (64.0%), hypothyroidism (57.4%) and diarrhea (54.2%) [ 16 , 92 ].…”

L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy

“…Lenvatinib is a small-molecule tyrosine kinase inhibitor (TKI) that targets multiple receptors, including vascular endothelial growth factor receptors (VEGFRs) 1–3, fibroblast growth factor receptors (FGFRs) 1–4, and platelet-derived growth factor receptor (PDGFR) α and β ( Matsui et al, 2008 ). Owing to its potent antineoplastic activity, lenvatinib has become a standard agent for the treatment of several types of advanced cancers such as hepatocellular carcinoma (HCC), differentiated thyroid carcinoma, and renal cell carcinoma ( Motzer et al, 2022 ). However, like other TKIs, lenvatinib often causes adverse drug reactions such as hypertension, diarrhea, proteinuria, and fatigue, which may lead to dose interruption or discontinuation ( Kudo et al, 2018 ), ( Kim et al, 2021 ).…”