JCO Early Release, published online ahead of print Jun 9 2008
Journal of Clinical Oncology, 10.1200/JCO.2008.16.3279
Received January 24, 2008
Accepted April 6, 2008
Phase II Trial of Sorafenib in Advanced Thyroid Cancer
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, and Marcia S. Brose*
From the Developmental Therapeutics Program of the Abramson Cancer Center and Departments of Medicine, Biostatistics and Epidemiology, Otorhinolaryngology: Head and Neck Surgery, and Radiology, University of Pennsylvania, Philadelphia, PA.
* To whom correspondence should be addressed. E-mail: brosem{at}mail.med.upenn.edu
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.
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