Phase II study of sunitinib (SU) in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor (NET).

Abstract

381 Background: SU is an oral, multitargeted, antiangiogenic, tyrosine kinase inhibitor effective in patients (pts) with unresectable, well-differentiated pancreatic NET. This open-label, phase II study examined whether SU is also effective in Japanese pts with this disease. Methods: Japanese pts received SU 37.5 mg/day on a continuous daily dosing (CDD) schedule (28-day cycle). The primary endpoint was clinical benefit rate (CBR; complete response [CR] + partial response [PR] + stable disease [SD] ≥24 weeks). Secondary endpoints included: objective response rate (ORR; CR + PR), 6-mos progression-free survival (PFS) probability, safety and pharmacokinetics. Tumor assessments were performed at baseline and 8-wk intervals by CT or MRI (RECIST). Results: Twelve patients were enrolled and received treatment (tx; median age 54 yrs, range 34–79); 9 were ongoing at data cut-off (July 1, 2011). CBR was 75.0% (95% CI 42.8, 94.5), comprising 5 PRs and 4 pts with SD ≥24 weeks. ORR was 41.7% (95% CI 15.2, 72.3). 6-mos PFS probability was 91.7% (95% CI 53.9, 98.8). One PR occurred in a pt with gastrinoma, in whom gastrin levels decreased by 93% and tumor bulk decreased by 45%. All-causality, any-grade (G) AEs included diarrhea (n=9, 75%), HFS and hypertension (both n=8, 67%). Neutropenia was the most common G3 AE (n=5, 42%, all tx-related). Three pts (25%) experienced G4 AEs (herpes encephalitis, convulsion, loss of consciousness [n=1] and lipase increased [n=2], all tx-related).Two pts (17%) experienced serious AEs: convulsion and loss of consciousness (n=1, tx-related), and acute cholecystitis (n=1, unrelated to tx). There were no deaths on study; one death due to disease progression occurred 3 mos after study withdrawal. On day 15 (cycle 1), mean trough plasma concentrations (n=10) for SU, its metabolite, and SU + metabolite were 53.9, 23.7 and 77.5 ng/mL, respectively. SU on a CDD schedule resulted in sustained drug concentrations without accumulation across cycles. Conclusions: SU 37.5 mg/day on a CDD schedule demonstrated antitumor activity in Japanese pts with unresectable, well-differentiated pancreatic NET. Common AEs were consistent with the known safety profile of SU.