Abstract
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.
Publication types
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Clinical Trial, Phase III
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Comparative Study
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Multicenter Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Aged, 80 and over
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / therapeutic use*
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Benzamides
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Disease-Free Survival
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Drug Resistance, Neoplasm
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Female
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Gastrointestinal Neoplasms / drug therapy*
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Gastrointestinal Neoplasms / mortality
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Gastrointestinal Neoplasms / pathology
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Gastrointestinal Stromal Tumors / drug therapy*
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Gastrointestinal Stromal Tumors / mortality
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Gastrointestinal Stromal Tumors / pathology
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Humans
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Imatinib Mesylate
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Indoles / adverse effects
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Indoles / pharmacology
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Indoles / therapeutic use*
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Kaplan-Meier Estimate
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Male
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Middle Aged
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Palliative Care
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Piperazines / adverse effects
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Piperazines / pharmacology
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Piperazines / therapeutic use*
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Protein Kinase Inhibitors / adverse effects
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / therapeutic use*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Pyrimidines / adverse effects
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Pyrimidines / pharmacokinetics
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Pyrimidines / pharmacology
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Pyrimidines / therapeutic use*
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Pyrroles / adverse effects
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Pyrroles / pharmacology
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Pyrroles / therapeutic use*
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Sunitinib
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Treatment Outcome
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Young Adult
Substances
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Antineoplastic Agents
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Benzamides
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Indoles
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Piperazines
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Protein Kinase Inhibitors
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Pyrimidines
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Pyrroles
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Imatinib Mesylate
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Protein-Tyrosine Kinases
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nilotinib
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Sunitinib