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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

Jean-Yves Blay, Axel Le Cesne, Isabelle Ray-Coquard, Binh Bui, Florence Duffaud, Catherine Delbaldo, Antoine Adenis, Patrice Viens, Maria Rios, Emmanuelle Bompas, Didier Cupissol, Cecile Guillemet, Pierre Kerbrat, Jérome Fayette, Sylvie Chabaud, Patrice Berthaud, David Perol

From the Unité INSERM U590 Centre Léon Bérard & Université Claude Bernard Lyon I & Hopital Edouard Herriot; Département de Médecine & UBET, Centre Léon Bérard; Hopital Edouard Herriot, Lyon; Institut Gustave Roussy, Villejuif; Institut Bergonié, Bordeaux; Hopital La Timone, Marseille; Centre Oscar Lambret, Lille; Institut Paoli Calmettes, Marseille; Centre Alexis Vautrin, Nancy; Centre René Gauducheau, Nantes; Centre Val D'Aurelle Montpellier; Centre Henri Becquerel, Rouen; and Novartis Pharma, Rueil Malmaison, France

Address reprint requests to Jean-Yves Blay, MD, INSERM U590, Centre Léon Bérard & Université Claude Bernard Lyon I & Unité d'Oncologie Médicale, Hôpital Edouard Herriot, 28, rue Laennec, 69008 Lyon, France; e-mail: blay{at}lyon.fnclcc.fr; or Axel Le Cesne, MD, Institut Gustave Roussy, Villejuif, France; e-mail: lecesne@igr.fr

Purpose: Imatinib is the standard treatment of advanced GI stromal tumors (GISTs). It is not known whether imatinib may be stopped in patients in whom disease is controlled.

Methods: This prospective, randomized, multicentric phase III study was designed to compare continuous (CONT) compared with interrupted (INT) imatinib beyond 1 year of treatment in patients with advanced GIST. The primary end point was progression-free survival. Secondary end points included overall survival, response rate after reinitiation of imatinib, and quality of life. Early stopping rules in cases of rapid progression of disease were defined, with preplanned interim analyses.

Results: Between May 2002 and April 2004, 182 patients with advanced GIST were enrolled. Between May 2003 and April 2004, 98 patients in response or stable disease under imatinib reached more than 1 year of follow-up. Forty were not eligible for randomization, and 58 patients were randomly assigned, 32 and 26 patients in the INT and CONT arms, respectively. As of October 15, 2005, eight of 26 patients in the CONT group and 26 of 32 patients in the INT group had documented disease progression (P < .0001). Twenty-four of 26 patients with documented progression in the INT arm responded to imatinib reintroduction. No differences in overall survival or imatinib resistance were observed between the two arms. Quality of life evaluated 6 months after random assignment using the 30-item Quality of Life Questionnaire was not significantly different between the two groups of randomly assigned patients.

Conclusion: Imatinib interruption results in rapid progression in most patients with advanced GIST, and cannot be recommended in routine practice unless patient experience significant toxicity.

Supported by grant from the 2003 Emergence Fund of the French Institut National du Cancer (INCa) through the Canceropole CLARA, an unrestricted grant of the Comité de l’Ain de la Ligue Contre Le Cancer, a Grant from the Comité du Rhône de la Ligue Contre Le Cancer, the CONTICANET Network of Excellence of the sixth Framework Program of the European Commission.

J.-Y.B. and A.L.C. contributed equally to this work.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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