DOVITINIB IN RESISTANT GISTs

Br J Cancer. 2013 Oct 29;109(9):2309-15. doi: 10.1038/bjc.2013.594. Epub 2013 Oct 1.

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

Kang YK, Yoo C, Ryoo BY, Lee JJ, Tan E, Park I, Park JH, Choi YJ, Jo J, Ryu JS, Ryu MH.

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Abstract

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, 500 mg 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 enrolled. 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.