Phase II trial of sorafenib in advanced thyroid cancer

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.

Fig 1.

Best overall percentage of change from baseline in target lesion measurement. Baseline radiographic measurements of target lesions were compared with measurements over the course of the study to determine the best change in target lesion size for each patient with data. RECIST, Response Evaluation Criteria in Solid Tumors; PD, progressive disease; SD, stable disease; PR, partial response; MTC, medullary thyroid cancer.

Fig 2.

Kaplan-Meier estimate of progression-free survival (PFS) for patients on study. Median PFS was 79.0 weeks.

Fig 3.

(A) A 60-year-old man with follicular thyroid cancer had metastatic disease in the lung (left). Computed tomography (CT) scans confirm partial response in target lesions (right) after 16 weeks of treatment with sorafenib. (B) A 59-year-old woman with papillary thyroid cancer had widespread miliary lung metastases (left). CT scans show marked improvement in the burden of lung disease after 33 weeks of treatment with sorafenib (right).