Phase II Trial of Sorafenib in Advanced Thyroid Cancer

• Published in: Journal of clinical oncology Vol. 26; no. 29; pp. 4714 - 4719
• Main Authors: GUPTA-ABRAMSON, Vandana, TROXEL, Andrea B, BROSE, Marcia S, NELLORE, Anoma, PUTTASWAMY, Kanchan, REDLINGER, Maryann, RANSONE, Kathy, MANDEL, Susan J, FLAHERTY, Keith T, LOEVNER, Laurie A, O'DWYER, Peter J
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 10.10.2008; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Benzenesulfonates - therapeutic use; Biological and medical sciences; Endocrinopathies; Female; Head and Neck Cancer; Humans; Male; Malignant tumors; Medical sciences; Middle Aged; Niacinamide - analogs & derivatives; Phenylurea Compounds; Pyridines - therapeutic use; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Tumors; Endocrinopathy; Antineoplastic agent; Tyrosine kinase inhibitor; Thyroid diseases; Enzyme inhibitor; Malignant tumor; Thyroid cancer; Cancerology; Sorafenib; Phase II trial; Advanced stage; Multikinase inhibitor; Antiangiogenic agent; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2008.16.3279

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. 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. 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. 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.