1479PD - Multi-Center Phase II Study of Sunitinib in Patients with Advanced Aggressive Fibromatosis (Desmoid Tumor)

Abstract

ABSTRACT Background There have been reports on the efficacy of imatinib, a multi-targeted tyrosine kinase inhibitor, in the treatment of aggressive fibromatosis (AF, also known as desmoid tumor) by inhibiting PDGFRA and PDGFRB rather than KIT. Sunitinib has not only PDGFRs, KIT, and FLT3 inhibiting activity but also VEGFRs blockade as antiangiogenesis. The aim of this study is to evaluate the efficacy and safety of sunitinib for patients with AF. Methods This is a multi-center, phase II study. Nineteen patients with pathologically proven AF were accrued between Jun 2008 and Mar 2012. Sunitinib was administered with 37.5 mg/day for 4 weeks without break, comprising one cycle. Primary endpoint was response rate. Results Ten (53%) patients were female and the median age was 30 years (range, 22-67). Most of the primary sites were intra-abdominal (12, 63%), and AF associated with familial adenomatous polyposis was observed in 9 (47%). The median tumor size was 5.0 cm (range, 2.0-14.2), and 8 patients (42.1) had multifocal tumor lesions. Of the 15 patients who received two or more cycles of treatment, 6 (40%) required dose reductions. With a median 5 cycles per patients (range, 1-47 cycles), 5 (26%) achieved a partial response and 8 (42%) had stable disease; the overall response rate was 26% (95% CI, 6.3-45.7). With median follow-up time of 11.8 months (range, 1.4-43.7), the 2-year progression-free survival and overall survival were 70% and 100%, respectively. Of 10 patients in whom thyroid function test were checked, 1 (10%) had grade 2 hypothyroidism and 5 (50%) grade 1. Grade 3 or 4 adverse events of sunitinib with frequency > 5% of patients included neutropenia (33%), diarrhea (5%), and hand-foot syndrome (5%). Intra-abdominal tumor perforation with cystic necrosis within first cycle of sunitinib occurred in 3 cases; 2 cases underwent palliative tumor resection and 1 case recovered with medical treatment. There was no treatment-related death. Conclusion Sunitinib was well-tolerated and showed promising antitumor activity in patients with AF. Further investigations on clinical and translational researches of sunitinib in these patients are warranted. Disclosure All authors have declared no conflicts of interest.