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


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.


CONCLUSIONS
Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer.
Section of Hematology/Oncology, Department of Medicine, University of Chicago Division of Biological Sciences, 5801 S Ellis, Chicago, IL 60637, USA. ecohen@medicine.bsd.uchicago.edu
Ezra E W
EE
Cohen
Lee S
LS
Rosen
Everett E
EE
Vokes
Merrill S
MS
Kies
Arlene A
AA
Forastiere
Francis P
FP
Worden
Madeleine A
MA
Kane
Eric
E
Sherman
Sinil
S
Kim
Paul
P
Bycott
Michael
M
Tortorici
David R
DR
Shalinsky
Katherine F
KF
Liau
Roger B
RB
Cohen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077784:Axitinib; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007191:Indazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D000077784:Axitinib; D040262:Receptors, Vascular Endothelial Growth Factor