title: Spotlight on lenvatinib in the treatment of thyroid cancer: patient selection and perspectives.
abstract: Thyroid cancer is the most common endocrine malignancy, with over 60,000 cases reported per year in the US alone. The incidence of thyroid cancer has increased in the last several years. Patients with metastatic differentiated thyroid cancer (DTC) generally have a good prognosis. Metastatic DTC can often be treated in a targeted manner with radioactive iodine, but the ability to accumulate iodine is lost with decreasing differentiation. Until recently, chemotherapy was the only treatment in patients with advanced thyroid cancer, which is no longer amenable to therapy with radioactive iodine. The modest efficacy and significant toxicity of chemotherapy necessitated the need for urgent advances in the medical field. New insights in thyroid cancer biology propelled the development of targeted therapies for this disease, including the tyrosine kinase inhibitor sorafenib as salvage treatment for DTC. In 2015, the US Food and Drug Administration approved a second tyrosine kinase inhibitor, lenvatinib, for the treatment of radioiodine-refractory thyroid cancer. Although associated with a significant progression-free survival improvement as compared to placebo in a large Phase III study (median progression-free survival 18.2 vs 3.6 months; hazard ratio 0.21; 99% confidence interval 0.14-0.31; P<0.001), the benefit of lenvatinib needs to be proved in the context of associated moderate to severe toxicities that require frequent dose reduction and delays. This article reviews the evidence supporting the use of lenvatinib as salvage therapy for radioactive iodine-refractory thyroid cancer, with a focus on the toxicity profile of this new therapy.
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, IL, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Costa
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, IL, USA; Division of Hematology and Oncology, Feinberg School of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Benedito A
authors.initials: BA
authors.lastname: Carneiro
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, IL, USA; Division of Hematology and Oncology, Feinberg School of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Sunandana
authors.initials: S
authors.lastname: Chandra
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, IL, USA.
authors.forename: Sachin G
authors.initials: SG
authors.lastname: Pai
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, IL, USA; Division of Hematology and Oncology, Feinberg School of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Young Kwang
authors.initials: YK
authors.lastname: Chae
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, IL, USA; Division of Hematology and Oncology, Feinberg School of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Kaplan
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, IL, USA.
authors.forename: Hannah B
authors.initials: HB
authors.lastname: Garrett
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, IL, USA; Division of Hematology and Oncology, Feinberg School of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Agulnik
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kopp
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, IL, USA; Division of Hematology and Oncology, Feinberg School of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D018579:Patient Selection; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D011505:Protein-Tyrosine Kinases; C531958:lenvatinib
keywords: differentiated thyroid cancer; lenvatinib; targeted therapy; thyroid cancer; tyrosine kinse inhibitor