Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study

Abstract

Purpose: Patients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine ((131)I) therapy have few satisfactory therapeutic options. This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer.

Patients and methods: Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I were enrolled onto a single-arm phase II trial to receive axitinib orally (starting dose, 5 mg twice daily). Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors was the primary end point. Secondary end points included duration of response, progression-free survival (PFS), overall survival, safety, and modulation of soluble (s) VEGFR.

Results: Sixty patients were enrolled. Partial responses were observed in 18 patients, yielding an ORR of 30% (95% CI, 18.9 to 43.2). Stable disease lasting > or = 16 weeks was reported in another 23 patients (38%).

Objective: responses were noted in all histologic subtypes. Median PFS was 18.1 months (95% CI, 12.1 to not estimable). Axitinib was generally well tolerated, with the most common grade > or = 3 treatment-related adverse event being hypertension (n = 7; 12%). Eight patients (13%) discontinued treatment because of adverse events. Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT, demonstrating its targeting of VEGFR.

Conclusion: Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer.

Fig 1.

Maximum percentage of tumor reduction for target lesions by Response Evaluation Criteria in Solid Tumors. The gray line represents zero change in tumor size. Each bar represents an individual patient. PR, partial response; SD, stable disease; PD, progressive disease.

Fig 2.

Kaplan-Meier curve for overall survival in patients with medullary thyroid cancer (solid line) and differentiated thyroid cancer (dashed line). Patients (n = 2) with anaplastic carcinoma or “other” histology (n = 2) were excluded from this analysis.

Fig 3.

(A) Preferential suppression of soluble vascular endothelial growth factor receptor (sVEGFR) −2 and sVEGFR-3 by axitinib in patients with thyroid cancer. (B) Percentage change in calcitonin from baseline. (C) Percentage change in thyroglobulin from baseline. PD, progressive disease; SD, stable disease; PR, partial response.