Phase III study of nilotinib versus best supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinib.

BACKGROUND: This phase III open-label trial investigated the efficacy of nilotinib in patients with advanced gastrointestinal stromal tumors following prior imatinib and sunitinib failure. PATIENTS AND METHODS: Patients were randomized 2:1 to nilotinib 400 mg b.i.d. or best supportive care (BSC; BSC without tyrosine kinase inhibitor, BSC+imatinib, or BSC+sunitinib). Primary efficacy end point was progression-free survival (PFS) based on blinded central radiology review (CRR). Patients progressing on BSC could cross over to nilotinib.
RESULTS: Two hundred and forty-eight patients enrolled. Median PFS was similar between arms (nilotinib 109 days, BSC 111 days; P=0.56). Local investigator-based intent-to-treat (ITT) analysis showed a significantly longer median PFS with nilotinib (119 versus 70 days; P=0.0007). A trend in longer median overall survival (OS) was noted with nilotinib (332 versus 280 days; P=0.29). Post hoc subset analyses in patients with progression and only one prior regimen each of imatinib and sunitinib revealed a significant difference in median OS of >4 months in favor of nilotinib (405 versus 280 days; P=0.02). Nilotinib was well tolerated.
CONCLUSION: In the ITT analysis, no significant difference in PFS was observed between treatment arms based on CRR. In the post hoc subset analyses, nilotinib provided significantly longer median OS.