Originally published as JCO Early Release 10.1200/JCO.2008.21.3330 on July 20 2009

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Absence of Progression As Assessed by Response Evaluation Criteria in Solid Tumors Predicts Survival in Advanced GI Stromal Tumors Treated With Imatinib Mesylate: The Intergroup EORTC-ISG-AGITG Phase III Trial

From the Institut Gustave Roussy, Villejuif; Institut Bergonié, Bordeaux; Centre Léon Bérard, Lyon, France; European Organisation for Research and Treatment of Cancer Headquarters, Brussels; UZ Gasthuisberg, Leuven, Belgium; Erasmus University Medical Center, Rotterdam; Leiden University Medical Center, Leiden, the Netherlands; Instituto dei Tumori, Milan, Italy; University of Auckland, Auckland, New Zealand; Helios Klinikum, Berlin-Buch; Klinikum Grosshaden Ludwig-Maximilians University, Muenchen, Germany; Royal Marsden Hospital, London, United Kingdom; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Corresponding author: Axel Le Cesne, MD, Department of Medicine, Institut Gustave Roussy, 94805 Villejuif Cedex, France; e-mail: lecesne{at}igr.fr.

Purpose From February 2001 to February 2002, 946 patients with advanced GI stromal tumors (GISTs) treated with imatinib were included in a controlled EORTC/ISG/AGITG (European Organisation for Research and Treatment of Cancer/Italian Sarcoma Group/Australasian Gastro-Intestinal Trials Group) trial. This analysis investigates whether the response classification assessed by RECIST (Response Evaluation Criteria in Solid Tumors), predicts for time to progression (TTP) and overall survival (OS).

Patients and Methods Per protocol, the first three disease assessments were done at 2, 4, and 6 months. For the purpose of the analysis (landmark method), disease response was subclassified in six categories: partial response (PR; > 30% size reduction), minor response (MR; 10% to 30% reduction), no change (NC) as either NC– (0% to 10% reduction) or NC+ (0% to 20% size increase), progressive disease (PD; > 20% increase/new lesions), and subjective PD (clinical progression).

Results A total of 906 patients had measurable disease at entry. At all measurement time points, complete response (CR), PR, and MR resulted in similar TTP and OS; this was also true for NC– and NC+, and for PD and subjective PD. Patients were subsequently classified as responders (CR/PR/MR), NC (NC+/NC–), or PD. This three-class response categorization was found to be highly predictive of further progression or survival for the first two measurement points. After 6 months of imatinib, responders (CR/PR/MR) had the same survival prognosis as patients classified as NC.

Conclusion RECIST perfectly enables early discrimination between patients who benefited long term from imatinib and those who did not. After 6 months of imatinib, if the patient is not experiencing PD, the pattern of radiologic response by tumor size criteria has no prognostic value for further outcome. Imatinib needs to be continued as long as there is no progression according to RECIST.

Supported by an unrestricted grant from Novartis Oncology for European Organisation for Research and Treatment of Cancer/Italian Sarcoma Group/Australasian Gastro-Intestinal Trials Group Clinical Trial 62005; by Grant No. 5U10 CA11488-37 (through 5U10 CA011488-38) from the National Cancer Institute, Bethesda, MD; and by funding from Fonds Cancer (FOCA) in Belgium.

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

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