Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma

Thyroid. 2017 Sep;27(9):1142-1148. doi: 10.1089/thy.2016.0621. Epub 2017 Jul 24.


Background: Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC.

Methods: Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent.

Results: A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7-5.6], and median OS was 5.0 months [confidence interval 0.7-5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%.

Conclusions: The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and radioactive iodine-refractory DTC.

Keywords: Phase II clinical trial; anaplastic thyroid carcinoma; medullary thyroid carcinoma; overall survival; progression-free survival; sorafenib.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Alopecia / chemically induced
  • Alopecia / ethnology
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Neuroendocrine / drug therapy*
  • Carcinoma, Neuroendocrine / ethnology
  • Carcinoma, Neuroendocrine / pathology
  • Carcinoma, Neuroendocrine / secondary
  • Diarrhea / chemically induced
  • Diarrhea / ethnology
  • Drug Resistance, Neoplasm
  • Female
  • Hand-Foot Syndrome / ethnology
  • Hand-Foot Syndrome / etiology
  • Humans
  • Hypertension / chemically induced
  • Hypertension / ethnology
  • Japan
  • Male
  • Neoplasm Grading
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Patient Dropouts / ethnology
  • Phenylurea Compounds / adverse effects*
  • Phenylurea Compounds / therapeutic use
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Sorafenib
  • Survival Analysis
  • Thyroid Carcinoma, Anaplastic / drug therapy*
  • Thyroid Carcinoma, Anaplastic / ethnology
  • Thyroid Carcinoma, Anaplastic / pathology
  • Thyroid Gland / drug effects*
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / ethnology
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / secondary
  • Tumor Burden / drug effects


  • Antineoplastic Agents
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Niacinamide
  • Sorafenib

Supplementary concepts

  • Thyroid cancer, medullary