Phase 2 study of nilotinib as third-line therapy for patients with gastrointestinal stromal tumor.

Abstract

BACKGROUND:

Patients with gastrointestinal stromal tumors (GISTs) resistant to both imatinib and sunitinib have a poor prognosis and few therapeutic options. In this study, the efficacy and safety of nilotinib (AMN107) as a third-line therapy for patients with GISTs was evaluated.

METHODS:

A single-arm, open-label trial was conducted in 8 Japanese hospitals. The key eligibility criteria included resistance or intolerance to both imatinib and sunitinib treatment. The primary endpoint was disease control rate, defined as the percentage of patients with complete response, partial response (PR), or stable disease (SD) lasting 24 weeks or longer.

RESULTS:

Thirty-five patients were enrolled and treated with nilotinib 400 mg twice daily, which generally was well tolerated. Disease control rate at Week 24 was 29% (90% confidence interval, 16.4%-43.6%). The median progression-free survival was 113 days, and the median overall survival was 310 days. The objective response rate was 3%, comprising 1 PR in a patient with a GIST possessing both a KIT exon 11 mutation, and an imatinib-resistant and sunitinib-resistant KIT exon 17 mutation. Twenty-three (66%) patients had SD (≥6 weeks) as the best response.

CONCLUSIONS:

These results suggest that nilotinib is generally well tolerated and has encouraging antitumor activity in patients with GIST who failed both imatinib and sunitinib.

• Authors: Akira Sawaki, Toshirou Nishida, Toshihiko Doi, Yasuhide Yamada, Yoshito Komatsu, Tatsuo Kanda, Yoshihiro Kakeji, Yusuke Onozawa, Makoto Yamasaki, Atsushi Ohtsu
• Journal: Cancer (Cancer) Vol. 117 Issue 20 Pg. 4633-41 (Oct 15 2011) ISSN: 1097-0142 [Electronic] United States
• PMID: 21456006 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Cancer Society.

Chemical References

• Antineoplastic Agents
• Benzamides
• Indoles
• Piperazines
• Pyrimidines
• Pyrroles
• Imatinib Mesylate
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-kit
• Receptor, Platelet-Derived Growth Factor alpha
• nilotinib
• Sunitinib

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Benzamides
• Disease-Free Survival
• Drug Administration Schedule
• Drug Resistance, Neoplasm (genetics)
• Female
• Gastrointestinal Stromal Tumors (drug therapy, genetics, pathology)
• Humans
• Imatinib Mesylate
• Indoles (pharmacology)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Mutation
• Neoplasm Grading
• Neoplasm Staging
• Piperazines (pharmacology)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Proto-Oncogene Proteins c-kit (genetics)
• Pyrimidines (administration & dosage, pharmacology, therapeutic use)
• Pyrroles (pharmacology)
• Receptor, Platelet-Derived Growth Factor alpha (genetics)
• Salvage Therapy (methods)
• Sunitinib
• Time Factors
• Treatment Outcome