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

P Reichardt; J-Y Blay; H Gelderblom; M Schlemmer; G D Demetri; B Bui-Nguyen; G A McArthur; S Yazji; Y Hsu; I Galetic; P Rutkowski

doi:10.1093/annonc/mdr598

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

Ann Oncol. 2012 Jul;23(7):1680-7. doi: 10.1093/annonc/mdr598. Epub 2012 Feb 21.

Authors

P Reichardt¹, J-Y Blay, H Gelderblom, M Schlemmer, G D Demetri, B Bui-Nguyen, G A McArthur, S Yazji, Y Hsu, I Galetic, P Rutkowski

Affiliation

¹ HELIOS Klinikum Bad Saarow, Sarkomzentrum Berlin-Brandenburg, Bad Saarow, Germany. peter.reichardt@helios-kliniken.de

PMID: 22357255
DOI: 10.1093/annonc/mdr598

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

Clinical Trial, Phase III
Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Agents / adverse effects
Antineoplastic Agents / pharmacokinetics
Antineoplastic Agents / therapeutic use*
Benzamides
Disease-Free Survival
Drug Resistance, Neoplasm
Female
Gastrointestinal Neoplasms / drug therapy*
Gastrointestinal Neoplasms / mortality
Gastrointestinal Neoplasms / pathology
Gastrointestinal Stromal Tumors / drug therapy*
Gastrointestinal Stromal Tumors / mortality
Gastrointestinal Stromal Tumors / pathology
Humans
Imatinib Mesylate
Indoles / adverse effects
Indoles / pharmacology
Indoles / therapeutic use*
Kaplan-Meier Estimate
Male
Middle Aged
Palliative Care
Piperazines / adverse effects
Piperazines / pharmacology
Piperazines / therapeutic use*
Protein Kinase Inhibitors / adverse effects
Protein Kinase Inhibitors / pharmacokinetics
Protein Kinase Inhibitors / therapeutic use*
Protein-Tyrosine Kinases / antagonists & inhibitors
Pyrimidines / adverse effects
Pyrimidines / pharmacokinetics
Pyrimidines / pharmacology
Pyrimidines / therapeutic use*
Pyrroles / adverse effects
Pyrroles / pharmacology
Pyrroles / therapeutic use*
Sunitinib
Treatment Outcome
Young Adult

Substances

Antineoplastic Agents
Benzamides
Indoles
Piperazines
Protein Kinase Inhibitors
Pyrimidines
Pyrroles
Imatinib Mesylate
Protein-Tyrosine Kinases
nilotinib
Sunitinib