Evaluation of nilotinib (N) in advanced GIST previously treated with imatinib mesylate (IM) and sunitinib (S).

10090 Background: Patients with advanced GIST progressing following IM and S often continue with good performance statuses and need additional therapy. This study tested the benefit of N, a second generation tyrosine kinase inhibitor that functions via ATP-competitive inhibition, developed to optimize binding to BCR-ABL for the therapy of chronic myelogenous leukemia. In vitro the agent can inhibit KIT and PDGFR phosphorylation, is active against IM-resistant cell lines and achieves higher intracellular concentrations compared to IM. Methods: This was a single center open label phase II study. The primary objective was to determine PFS at 6 months. Using a novel statistical design (S. Litwin et al, 2008), 17 patients were to be enrolled; if 10 or more were progression free (PF) at 2 months an additional 19 patients would be enrolled. The therapy was considered of benefit if greater than 13 patients were PF at 6 months. All patients signed informed consents and entry criteria included normal cardiac functi...