A prospective multicenter phase II study of sunitinib in patients with advanced aggressive fibromatosis.

Abstract

10589 Background: There have been reports on responses and prolonged disease stabilizations with imatinib which may be associated with PDGFR-β pathway and KIT mutation in the treatment of aggressive fibromatosis (AF). 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 advanced AF. Methods: 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, 63.2%), and AF associated with familial adenomatous polyposis was observed in 10 (52.6%). With a median 6 cycles per patients (range, 1-47 cycles), 5 (26.3%) achieved a partial response and 8 (42.1%) had stable disease; the overall response rate was 26.3% (95% CI, 6.3-45.7) in intention-to-treat analysis. With median follow-up time of 20.3 months (range, 1.8-50.7), the 2-year progression-free survival and overall survival were 74.7% and 94.4%, respectively. Grade 3 or 4 adverse events of sunitinib with frequency > 5% of patients included neutropenia (33.3%), diarrhea (5.3%), and hand-foot syndrome (5.3%). In 3 patients out of 12 patients with mesenteric AF, mesenteric mass bleeding (n=1), bowel perforation (n=1), and bowel fistula (n=1) with tumor mass necrosis, were observed during an early period of sunitinib. Conclusions: Sunitinib showed potential antitumor activity and was relatively tolerated in patients with AF, especially non-mesenteric AF. Further investigation of sunitinib treatment is necessary in patients with AF.