A Phase II trial of axitinib in patients with various histologic subtypes of advanced thyroid cancer: long-term outcomes and pharmacokinetic/pharmacodynamic analyses

PURPOSE: Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, has shown activity in advanced thyroid cancer in a Phase II study. We report updated overall survival and pharmacokinetic/pharmacodynamic (PK/PD) analyses from the study. METHODS: Patients (N = 60) with advanced thyroid cancer of any histology for whom iodine-131 ((131)I) failed to control the disease or (131)I was not appropriate therapy were administered axitinib 5 mg twice daily. Objective response rate (primary endpoint), duration of response, progression-free survival, overall survival, safety, and PK/PD relationships were assessed. RESULTS: Objective response rate was 38 % [23 partial responses; 95 % confidence interval (CI) 26–52], and 18 (30 %) patients had stable disease lasting ≥16 weeks. Responses occurred in all histologic subtypes. With median follow-up of 34 months (95 % CI 32–37), median overall survival was 35 months (95 % CI 19–not estimable), median progression-free survival was 15 months (95 % CI 10–20), and median duration of response was 21 months (95 % CI 13–46). Most common Grade 3/4 treatment-related adverse events included hypertension (13 %), proteinuria (8 %), diarrhea (7 %), weight decrease (7 %), and fatigue (5 %). PK/PD analyses revealed trends toward greater tumor size reduction and response probability with higher axitinib plasma exposures. CONCLUSIONS: Axitinib appears active and well tolerated in patients with various histologic subtypes of advanced thyroid cancer, demonstrating durable responses and long overall survival. Axitinib may be useful for the treatment of advanced thyroid cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00280-014-2604-8) contains supplementary material, which is available to authorized users.