Tyrosine kinase inhibitor treatments in patients with metastatic thyroid carcinomas: a retrospective study of the TUTHYREF network

Eur J Endocrinol. 2014 Mar 8;170(4):575-82. doi: 10.1530/EJE-13-0825. Print 2014 Apr.

Abstract

Objective: Tyrosine kinase inhibitors (TKIs) are used to treat patients with advanced thyroid cancers. We retrospectively investigated the efficacy of TKIs administered outside of clinical trials in metastatic sites or locally advanced thyroid cancer patients from five French oncology centers.

Design and methods: THERE WERE 62 PATIENTS (37 MEN, MEAN AGE: 61 years) treated with sorafenib (62%), sunitinib (22%), and vandetanib (16%) outside of clinical trials; 22 had papillary, five had follicular, five had Hürthle cell, 13 had poorly differentiated, and 17 had medullary thyroid carcinoma (MTC). Thirty-three, 25, and four patients were treated with one, two, and three lines of TKIs respectively. Primary endpoints were objective tumor response rate and progression-free survival (PFS). Sequential treatments and tumor response according to metastatic sites were secondary endpoints.

Results: Among the 39 sorafenib and 12 sunitinib treatments in differentiated thyroid carcinoma (DTC) patients, partial response (PR) rate was 15 and 8% respectively. In the 11 MTC patients treated with vandetanib, 36% had PR. Median PFS was similar in second-line compared with first-line sorafenib or sunitinib therapy (6.7 vs 7.0 months) in DTC patients, but there was no PR with second- and third-line treatments. Bone and pleural lesions were the most refractory sites to treatment.

Conclusions: This is the largest retrospective study evaluating TKI therapies outside of clinical trials. DTC patients treated with second-line therapy had stable disease as best response, but had a similar median PFS compared with the first-line treatment.

Publication types

  • Observational Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / secondary
  • Adenocarcinoma, Follicular / drug therapy
  • Adenocarcinoma, Follicular / secondary
  • Adenoma, Oxyphilic
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary
  • Carcinoma / drug therapy
  • Carcinoma / secondary
  • Carcinoma, Neuroendocrine
  • Carcinoma, Papillary
  • Disease-Free Survival
  • Female
  • Humans
  • Indoles / therapeutic use*
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use*
  • Piperidines / therapeutic use*
  • Pleural Neoplasms / drug therapy
  • Pleural Neoplasms / secondary
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrroles / therapeutic use*
  • Quinazolines / therapeutic use*
  • Retrospective Studies
  • Sorafenib
  • Sunitinib
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / secondary
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Indoles
  • Phenylurea Compounds
  • Piperidines
  • Pyrroles
  • Quinazolines
  • Niacinamide
  • Sorafenib
  • Protein-Tyrosine Kinases
  • Sunitinib
  • N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine

Supplementary concepts

  • Thyroid cancer, Hurthle cell
  • Thyroid cancer, medullary