Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study

J Clin Oncol. 2008 Oct 10;26(29):4708-13. doi: 10.1200/JCO.2007.15.9566. Epub 2008 Jun 9.


Purpose: Patients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine ((131)I) therapy have few satisfactory therapeutic options. This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer.

Patients and methods: Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I were enrolled onto a single-arm phase II trial to receive axitinib orally (starting dose, 5 mg twice daily). Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors was the primary end point. Secondary end points included duration of response, progression-free survival (PFS), overall survival, safety, and modulation of soluble (s) VEGFR.

Results: Sixty patients were enrolled. Partial responses were observed in 18 patients, yielding an ORR of 30% (95% CI, 18.9 to 43.2). Stable disease lasting > or = 16 weeks was reported in another 23 patients (38%).

Objective: responses were noted in all histologic subtypes. Median PFS was 18.1 months (95% CI, 12.1 to not estimable). Axitinib was generally well tolerated, with the most common grade > or = 3 treatment-related adverse event being hypertension (n = 7; 12%). Eight patients (13%) discontinued treatment because of adverse events. Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT, demonstrating its targeting of VEGFR.

Conclusion: Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Axitinib
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Indazoles / therapeutic use*
  • Male
  • Middle Aged
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / pathology*


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Imidazoles
  • Indazoles
  • Axitinib
  • Receptors, Vascular Endothelial Growth Factor