Phase II trial of sorafenib in advanced thyroid cancer.

Authors

• Vandana Gupta-Abramson
• Andrea B Troxel
• Anoma Nellore
• Kanchan Puttaswamy
• Maryann Redlinger
• Kathy Ransone
• Susan J Mandel
• Keith T Flaherty
• Laurie A Loevner
• Peter J O'Dwyer
• Marcia S Brose

Publication/Presentation Date

10-10-2008

Abstract

PURPOSE: Given the molecular pathophysiology of thyroid cancer and the spectrum of kinases inhibited by sorafenib, including Raf kinase, vascular endothelial growth factor receptors, platelet-derived growth factor receptor, and RET tyrosine kinases, we conducted an open-label phase II trial to determine the efficacy of sorafenib in patients with advanced thyroid carcinoma.

PATIENTS AND METHODS: Eligible patients with metastatic, iodine-refractory thyroid carcinoma received sorafenib 400 mg orally twice daily. Responses were measured radiographically every 2 to 3 months. The study end points included response rate, progression-free survival (PFS), and best response by Response Evaluation Criteria in Solid Tumors.

RESULTS: Thirty patients were entered onto the study and treated for a minimum of 16 weeks. Seven patients (23%; 95% CI, 0.10 to 0.42) had a partial response lasting 18+ to 84 weeks. Sixteen patients (53%; 95% CI, 0.34 to 0.72) had stable disease lasting 14 to 89+ weeks. Seventeen (95%) of 19 patients for whom serial thyroglobulin levels were available showed a marked and rapid response in thyroglobulin levels with a mean decrease of 70%. The median PFS was 79 weeks. Toxicity was consistent with other sorafenib trials, although a single patient died of liver failure that was likely treatment related.

CONCLUSION: Sorafenib has clinically relevant antitumor activity in patients with metastatic, iodine-refractory thyroid carcinoma, with an overall clinical benefit rate (partial response + stable disease) of 77%, median PFS of 79 weeks, and an overall acceptable safety profile. These results represent a significant advance over chemotherapy in both response rate and PFS and support further investigation of this agent in these patients.

Volume

26

Issue

29

First Page

4714

Last Page

4719

ISSN

1527-7755

Published In/Presented At

Gupta-Abramson, V., Troxel, A. B., Nellore, A., Puttaswamy, K., Redlinger, M., Ransone, K., Mandel, S. J., Flaherty, K. T., Loevner, L. A., O'Dwyer, P. J., & Brose, M. S. (2008). Phase II trial of sorafenib in advanced thyroid cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 26(29), 4714–4719. https://doi.org/10.1200/JCO.2008.16.3279

Disciplines

Medicine and Health Sciences

PubMedID

18541894

Department(s)

Hematology-Medical Oncology Division

Document Type

Article