Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: An open-label multicentre randomised phase 3 trial

Axel Le Cesne, Isabelle Ray-Coquard, Binh Nguyen Bui, Antoine Adenis, Maria Rios, François Bertucci, Florence Duffaud, Christine Chevreau, Didier Cupissol, Angela Cioffi, Jean François Emile, Sylvie Chabaud, David Pérol, Jean Yves Blay

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    Résumé

    Background: The effect of imatinib discontinuation on progression-free survival and overall survival in long-lasting responders with advanced gastrointestinal stromal tumours (GIST) is unknown. We assessed treatment interruption in patients with non-progressive disease according to the Response Evaluation Criteria In Solid Tumors criteria after 3 years of imatinib in a randomised trial. Methods: In this open-label national multicentre phase 3 study in France, patients with GIST free of progression after 3 years of imatinib 400 mg/day were randomly assigned to continue or interrupt imatinib. Randomisation was done centrally and independently from other study procedures with computer-generated permuted blocks of two and four patients stratified by participating centre and presence or absence of residual disease on CT scan. The primary endpoint was progression-free survival. An interim analysis was planned after the first 50 randomly assigned patients. Analysis was done according to the intention-to-treat principle-ie, all patients randomly assigned to a study group were included. This study is registered with ClinicalTrial.gov, number NCT00367861. Findings: 434 patients were enrolled in this trial between May 27, 2002, and May 5, 2009. Between June 13, 2005, and May 30, 2007, 50 patients with non-progressive disease who had received 3 years of treatment with imatinib were randomly assigned to continue or interrupt their treatment, 25 patients in each group. By Dec 7, 2009, after a median follow-up of 35 months (95% CI 33-38) after random assignment, 2-year progression-free survival was 80% (95% CI 58-91) in the continuation group and 16% (5-33) in the interruption group (p<0·0001). There was no difference in adverse events grade 3 or greater (oedema and asthenia) between the two groups. Interpretation: Imatinib interruption after 3 years in responders results in a high risk of rapid progression in patients with advanced GIST. Discontinuation of imatinib is not recommended outside clinical trials unless patients experience significant toxic effects. Funding: Conticanet, the Ligue Contre Le Cancer du Rhone, and Novartis.

    langue originaleAnglais
    Pages (de - à)942-949
    Nombre de pages8
    journalThe Lancet Oncology
    Volume11
    Numéro de publication10
    Les DOIs
    étatPublié - 1 oct. 2010

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