Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure

Aims: To assess the antitumour activity, safety, pharmacokinetics and pharmacodynamics of continuous daily sunitinib dosing in patients with imatinib-resistant/intolerant gastrointestinal stromal tumour (GIST) and to assess morning dosing versus evening dosing. Patients and methods: In this open-label phase II study, patients were randomised to receive morning or evening dosing of sunitinib 37.5 mg/day. The primary end-point was clinical benefit rate (CBR; percent complete responses + partial responses [PRs] + stable disease [SD] >= 24 weeks). Secondary end-points included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters and plasma biomarker levels. Results: Sixty of 61 planned patients received treatment (30 per dosing group); 26 completed the study. overall, the CBR was 53% (95% exact CI, 40-66): eight patients (13%) achieved objective PRs; 24 (40%) achieved SD >= 24 weeks. Median PFS was 34 weeks (95% CI, 24-49); median OS was 107 weeks (95% CI, 72 - not yet calculable). Most adverse events (AEs) were of grade 1 or 2 in severity, and were manageable through dose modification or standard interventions. No new AEs were apparent compared with the approved intermittent dosing schedule. Antitumour activity and safety were generally similar with morning and evening dosing. Continuous daily sunitinib dosing achieved and sustained effective drug concentrations without additional accumulation across cycles. Decreases from baseline in plasma levels of soluble KIT after 20 and 24 weeks of dosing correlated with longer OS. Conclusion: For patients with imatinib-resistant/intolerant GIST, continuous daily sunitinib dosing appears to be an active alternative dosing strategy with acceptable safety. (c) 2009 Published by Elsevier Ltd.