Phase II study of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib

Background: This prospective, phase II trial evaluated the efficacy and safety of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours (GISTs) after failure of at least imatinib and sunitinib. Methods: Patients received oral dovitinib, 500mg once daily, for 5 consecutive days, followed by a 2-day rest, every 28 days. The primary endpoint was disease control rate (DCR; objective response + stable disease (SD)) at 24 weeks, assessed by computed tomography (CT) scan according to RECIST v1.0. Metabolic response was evaluated by positron emission tomography (PET)-CT scans performed at baseline and after 4 weeks of treatment. Results: Between September 2011 and April 2012, 30 patients were enroled. DCR at 24 weeks by RECIST v1.0 was 13% and one patient (3%) had a partial response. Based on the European Organization for Research and Treatment of Cancer PET response criteria, four patients (13%) had a metabolic partial response after 4 weeks of treatment. At a median follow-up of 8.3 months (range, 6.3-12.2 months), median progression-free survival (PFS) was 3.6 months (95% confidence interval (CI), 3.5-3.7 months) and median overall survival was 9.7 months (95% CI, 6.0-13.4 months). Metabolic progressive disease at Week 4 was significantly associated with shorter PFS (P = 0.03). Grade 3/4 adverse events included asthenia (20%), neutropenia (13%), thrombocytopenia (10%), and hypertriglyceridaemia (10%). Most toxicities were manageable by dose modification. Conclusion: Dovitinib showed modest antitumour activity with manageable toxicities in heavily pretreated patients with advanced GISTs.