Originally published as JCO Early Release 10.1200/JCO.2007.15.9566 on June 9 2008
Journal of Clinical Oncology, Vol 26, No 29 (October 10), 2008: pp. 4708-4713
© 2008 American Society of Clinical Oncology.
Axitinib Is an Active Treatment for All Histologic Subtypes of Advanced Thyroid Cancer: Results From a Phase II Study
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
From the University of Chicago, Chicago, IL; Premiere Oncology, Santa Monica; Pfizer Inc, San Diego, CA; M.D. Anderson Cancer Center, Houston, TX; Johns Hopkins University School of Medicine, Baltimore, MD; University of Michigan, Ann Arbor, MI; University of Colorado, Denver, CO; and Fox Chase Cancer Center, Philadelphia, PA
Corresponding author: Ezra E.W. Cohen, MD, Section of Hematology/Oncology, Department of Medicine, University of Chicago Division of Biological Sciences, 5801 S Ellis, Chicago, IL 60637; e-mail: ecohen{at}medicine.bsd.uchicago.edu
Purpose Patients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine (131I) 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 131I 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  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 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.
published online ahead of print at www.jco.org on June 9, 2008.
Supported by Pfizer Inc, La Jolla Laboratories, Clinical Development Department, San Diego, CA (institutional grant support to E.E.W.C., L.S.R., M.S.K., E.S., R.B.C.).
Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.
Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Clinical trial information can be found for the following: NCT00094055
[ClinicalTrials.gov]
.
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