title: Lenvatinib for Anaplastic Thyroid Cancer.
abstract: BACKGROUND
  Lenvatinib has been approved by regulatory agencies in Japan, the United States, and the European Union for treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thyroid cancer, however, is a clinically diverse disease that includes anaplastic thyroid cancer (ATC), the subtype associated with the highest lethality. Effective therapy for ATC is an unmet need.
  
  
  METHODS
  This phase 2, single-arm, open-label study in patients with thyroid cancer, including ATC, RR-DTC, and medullary thyroid cancer was conducted from 3 September 2012 to 9 July 2015. Patients received lenvatinib 24 mg daily until disease progression or development of unacceptable toxicity. The primary endpoint was safety, and the secondary endpoint was efficacy, as assessed by progression-free survival (PFS), overall survival (OS), and objective response rate.
  
  
  RESULTS
  At data cutoff, 17 patients with ATC were enrolled. All experienced ≥1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were decreased appetite (82%), hypertension (82%), fatigue (59%), nausea (59%), and proteinuria (59%). Of note, only one patient required lenvatinib withdrawal because of a TEAE, and this TEAE was considered unrelated to lenvatinib. The median PFS was 7.4 months [95% confidence interval (CI): 1.7-12.9], the median OS was 10.6 months (95% CI: 3.8-19.8), and the objective response rate was 24%.
  
  
  CONCLUSIONS
  In this study, lenvatinib demonstrated manageable toxicities with dose adjustments and clinical activity in patients with ATC. This clinical activity of lenvatinib warrants further investigation in ATC.
  
  
  BACKGROUND
  NCT01728623.
authors.affiliation: Department of Head and Neck Medical Oncology, National Cancer Center Hospital East , Kashiwa , Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tahara
authors.affiliation: Department of Medical Oncology and Hematology, Kobe University Hospital , Kobe , Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kiyota
authors.affiliation: Department of Head and Neck Medical Oncology, National Cancer Center Hospital East , Kashiwa , Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Department of Medical Oncology and Hematology, Kobe University Hospital , Kobe , Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Chayahara
authors.affiliation: Department of Medical Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research , Tokyo , Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakano
authors.affiliation: Department of Medical Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research , Tokyo , Japan.
authors.forename: Lina
authors.initials: L
authors.lastname: Inagaki
authors.affiliation: Department of Head and Neck Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research , Tokyo , Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Toda
authors.affiliation: Department of Head and Neck Medical Oncology, National Cancer Center Hospital East , Kashiwa , Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Enokida
authors.affiliation: Department of Medical Oncology and Hematology, Kobe University Hospital , Kobe , Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
authors.affiliation: Department of Medical Oncology and Hematology, Kobe University Hospital , Kobe , Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Eisai Co. Ltd. , Tokyo , Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Eisai Co. Ltd. , Tokyo , Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Eisai Co. Ltd. , Tokyo , Japan.
authors.forename: Katsuki
authors.initials: K
authors.lastname: Fujino
authors.affiliation: Eisai Inc. , Woodcliff Lake, NJ , USA.
authors.forename: Corina E
authors.initials: CE
authors.lastname: Dutcus
authors.affiliation: Department of Medical Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research , Tokyo , Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Takahashi
keywords: anaplastic thyroid cancer; clinical trial; lenvatinib; phase 2; tyrosine kinase inhibitor