Axitinib is an Active Treatment for All Histologic Subtypes of Advanced Thyroid Cancer: Results from a Phase II Study

Overview

Journal J Clin Oncol

Specialty Oncology

Date 2008 Jun 11

PMID 18541897

Citations 235

Authors

Ezra E W Cohen

Lee S Rosen

Everett E Vokes

Merrill S Kies

Arlene A Forastiere

Francis P Worden

Madeleine A Kane

Eric Sherman

Sinil Kim

Paul Bycott

Michael Tortorici

David R Shalinsky

Katherine F Liau

Roger B Cohen

Affiliations

Soon will be listed here.

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.

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