Lenvatinib in Advanced, Radioactive Iodine-Refractory, Differentiated Thyroid Carcinoma.
Management options are limited for patients with radioactive iodine refractory, locally advanced, or metastatic differentiated thyroid carcinoma. Prior to 2015, sorafenib, a multitargeted tyrosine kinase inhibitor, was the only approved treatment and was associated with a median progression-free survival (PFS) of 11 months and overall response rate (ORR) of 12% in a phase III trial. Lenvatinib, a multikinase inhibitor with high potency against VEGFR and FGFR demonstrated encouraging results in phase II trials. Recently, the pivotal SELECT trial provided the basis for the FDA approval of lenvatinib as a second targeted therapy for these patients. Median PFS of 18.3 months in the lenvatinib group was significantly improved from 3.6 months in the placebo group, with an HR of 0.21 (95% confidence interval, 0.4-0.31; P < 0.0001). ORR was also significantly increased in the lenvatinib arm (64.7%) compared with placebo (1.5%). In this article, we will review the molecular mechanisms of lenvatinib, the data from preclinical studies to the recent phase III clinical trial, and the biomarkers being studied to further guide patient selection and predict treatment response.
Division of Hematology/Oncology, Department of Medicine, UCSD Moores Cancer Center, La Jolla, California.
Kay T
KT
Yeung
Solid Tumor Therapeutics Program, UCSD Moores Cancer Center, La Jolla, California. ecohen@ucsd.edu.
Ezra E W
EE
Cohen
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D011836:Radiation Tolerance; D019233:Retreatment; D015398:Signal Transduction / Q000187:drug effects; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C531958:lenvatinib