Prospective Multicentric Randomized Study of Glivec® in Advanced GIST Expressing C-kit: Interruption After 5 Years vs Maintenance

Summary

Gastrointestinal stromal tumors (GISTs) are associated with a dismal prognosis in localized and advanced phase with a major resistance to conventional chemotherapy agents. Virtually all malignant GISTs actually harbor activating mutations of the KIT pathway in the tumor cells, leading to ligand-independent activation of KIT tyrosine kinase activity and tumor growth in vitro. Glivec® inhibits KIT and exerts a major antitumor efficacy in vivo in patients with advanced GIST. Glivec® is generally pursued until progression or intolerance. The optimal duration of treatment with Glivec® remains unknown. The objective of this study is to determine the feasibility of Glivec® treatment interruption with reintroduction at progression in GIST patients.

Timeline

Start

2002-05

Primary completion

2012-04

Completion

2013-05

Publications

• Background Le Cesne A, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Cioffi A, Emile JF, Chabaud S, Perol D, Blay JY; French Sarcoma Group. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010 Oct;11(10):942-9. doi: 10.1016/S1470-2045(10)70222-9. Epub 2010 Sep 21.
• Background Blay JY, Le Cesne A, Ray-Coquard I, Bui B, Duffaud F, Delbaldo C, Adenis A, Viens P, Rios M, Bompas E, Cupissol D, Guillemet C, Kerbrat P, Fayette J, Chabaud S, Berthaud P, Perol D. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007 Mar 20;25(9):1107-13. doi: 10.1200/JCO.2006.09.0183.
• Background Patrikidou A, Chabaud S, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Domont J, Perol D, Blay JY, Le Cesne A; French Sarcoma Group. Influence of imatinib interruption and rechallenge on the residual disease in patients with advanced GIST: results of the BFR14 prospective French Sarcoma Group randomised, phase III trial. Ann Oncol. 2013 Apr;24(4):1087-93. doi: 10.1093/annonc/mds587. Epub 2012 Nov 21.
• Background Blesius A, Cassier PA, Bertucci F, Fayette J, Ray-Coquard I, Bui B, Adenis A, Rios M, Cupissol D, Perol D, Blay JY, Le Cesne A. Neoadjuvant imatinib in patients with locally advanced non metastatic GIST in the prospective BFR14 trial. BMC Cancer. 2011 Feb 15;11:72. doi: 10.1186/1471-2407-11-72.
• Background Blay JY, Perol D, Le Cesne A. Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors. Ann Oncol. 2012 Jul;23(7):1659-65. doi: 10.1093/annonc/mdr622. Epub 2012 Feb 21.
• Blay JY, Devin Q, Duffaud F, Toulmonde M, Firmin N, Collard O, Bompas E, Verret B, Ray-Coquard I, Salas S, Henon C, Honore C, Brahmi M, Dufresne A, Pracht M, Hervieu A, Penel N, Bertucci F, Rios M, Saada-Bouzid E, Soibinet P, Perol D, Chabaud S, Italiano A, Cesne AL. Discontinuation versus continuation of imatinib in patients with advanced gastrointestinal stromal tumours (BFR14): exploratory long-term follow-up of an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2024 Sep;25(9):1163-1175. doi: 10.1016/S1470-2045(24)00318-8. Epub 2024 Aug 7.
• Patrikidou A, Domont J, Chabaud S, Ray-Coquard I, Coindre JM, Bui-Nguyen B, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Perol D, Emile JF, Blay JY, Le Cesne A; French Sarcoma Group. Long-term outcome of molecular subgroups of GIST patients treated with standard-dose imatinib in the BFR14 trial of the French Sarcoma Group. Eur J Cancer. 2016 Jan;52:173-80. doi: 10.1016/j.ejca.2015.10.069. Epub 2015 Dec 11.

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Indications