Phase 2 study of sunitinib in refractory thyroid cancer

Abstract

6025 Background: Few treatment options exist for patients with refractory differentiated (including papillary, follicular, and Hurthle cell) and medullary thyroid cancers (DTC and MTC, respectively). Recent data suggest that thyroid cancers respond to antiangiogenic agents; in addition a subgroup of thyroid cancers harbor activating alterations in the RET gene. Sunitinib, has inhibitory activity against RET, VEGFR, and PDGFR, and thus has potential to be active in both DTC and MTC. Methods: Adult patients with DTC or MTC, refractory to curative treatment (surgery, external beam radiotherapy, or radioactive iodine (RAI) were required to have evidence of progressive disease within 6 months of study entry, ECOG performance status 0–2, and normal organ and bone marrow function. Treatment consisted of 6 week cycles of sunitinib malate 50 mg QD on a 4-week on/2-week off schedule. Primary endpoint was RECIST and biochemical response rate. Results: 43 subjects (37 DTC, 6 MTC) were enrolled; 25 male, 18 female; median age 58. 34/37 DTC subjects received prior RAI. 6 subjects received prior systemic therapy. 22 and 21 subjects had ECOG PS 0 and 1, respectively. The most common drug related adverse events and incidence included fatigue (79%), diarrhea (56%), palmar-plantar erythrodysesthesia (53%), neutropenia (49%), and hypertension (42%). Grade 3–4 toxicity included neutropenia (26%), thrombocytopenia (16%), hypertension (16%), fatigue (14%), palmar-plantar erythrodysesthesia (14%), and gastrointestinal tract events (14%, 2 diarrhea, 1 tracheo-esophageal fistula, 1 gastric hemorrhage, 1 gastric ulcer, and 1 gastritis). Best response in 31 evaluable DTC patients who completed 2 cycles was PR 13%, SD 68%, PD 10%, and NE 13%. Best response in MTC patients was SD 83%, PD 17%. Conclusions: In patients with refractory DTC or MTC who have evidence of progressive disease, sunitinib at the 50 mg 4/2 schedule is able to induce responses or disease stabilization in the great majority. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer