New Therapies for Thyroid Cancer

Barbara A. Murphy, MD

Disclosures

Journal Watch. 2008;7(12) 

Sorafenib and axitinib demonstrated activity against recurrent and metastatic disease.

Summary

Only a minority of thyroid cancer patients develop locally recurrent or metastatic disease that is not curable with local therapy or I-131 treatment. However, treatment options for this small cohort have been limited; the only FDA-approved chemotherapy agent for thyroid cancer is adriamycin, which has shown only modest efficacy. Fortunately, our understanding of thyroid cancer's underlying biology has grown dramatically during the past decade, and this advancement has opened the way to investigation of targeted agents and identification of new therapies. Researchers now report results of two phase II studies of potentially active oral agents.

In one trial, investigators evaluated the efficacy of sorafenib (Nexavar), a multikinase inhibitor that blocks vascular endothelial growth factor (VEGF) and B-Raf signaling pathways, both of which are implicated in thyroid cancer. The researchers assessed outcomes in 30 patients with advanced thyroid cancer deemed incurable (18 papillary, 9 follicular/Hµrthle cell, 2 anaplastic/poorly differentiated, 1 medullary) who received sorafenib (400 mg twice daily). Tumor measurements were repeated at 8 weeks, at 16 weeks, and at 12-week intervals thereafter. Median progression-free survival (PFS) was 79 weeks. Seven patients (23%) achieved partial responses (PRs), and 16 patients (53%) had stable disease. Patients with anaplastic/poorly differentiated carcinomas had no responses; the patient with medullary thyroid cancer had stable disease. Toxicity was substantial: 6 patients (20%) discontinued therapy because of toxicity, 14 (47%) required dose reductions, and 10 (33%) required adjustments of their thyroid hormone therapy as a result of thyroid-stimulating hormone (TSH) levels that rose above 0.10 mU/L.

In a second trial, investigators evaluated axitinib (an oral VEGF inhibitor) in 60 patients with advanced thyroid cancer (30 papillary, 15 follicular [11 Hµrthle cell variant], 11 medullary, 2 anaplastic, 2 other). Patients had incurable disease with no evidence of hemoptysis, central pulmonary lesions, or hypertension. Patients received axitinib (5 mg twice daily; dose increased to 7 mg twice daily in the absence of grade 2 toxicity or blood pressure elevation >150/90 mm Hg). Tumors were measured every 8 weeks. Median PFS was 18.1 months. Eighteen patients (30%) experienced PRs, and 23 (43%) had stable disease. Responses were noted for all pathologic subtypes. Eight patients (13%) discontinued therapy because of toxicity. Fifteen patients were not eligible for response: 8 did not meet response criteria, and 7 had no post-baseline data.

Comment

The role of medical oncologists in the treatment of thyroid cancer has been limited because of the paucity of effective systemic agents. This situation is destined to improve now that a number of targeted agents have demonstrated moderate activity in recurrent and metastatic disease. Responses to axitinib in patients with Hürthle cell, medullary, and anaplastic/poorly differentiated thyroid tumor subtypes are especially noteworthy because these tumors have been refractory to systemic chemotherapy.

— Barbara A. Murphy, MD


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