Paolo G Casali1, Axel Le Cesne2, Andres Poveda Velasco2, Dusan Kotasek2, Piotr Rutkowski2, Peter Hohenberger2, Elena Fumagalli2, Ian R Judson2, Antoine Italiano2, Hans Gelderblom2, Antoine Adenis2, Jörg T Hartmann2, Florence Duffaud2, David Goldstein2, Javier M Broto2, Alessandro Gronchi2, Angelo P Dei Tos2, Sandrine Marréaud2, Winette T A van der Graaf2, John R Zalcberg2, Saskia Litière2, Jean-Yves Blay2. 1. Paolo G. Casali, Elena Fumagalli, and Alessandro Gronchi, Fondazione Istituto di Recovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milano; Angelo P. Dei Tos, Azienda Unità Locale Socio Sanitaria 9 Treviso, Treviso, Italy; Axel Le Cesne, Gustave Roussy, Villejuif; Antoine Italiano, Institut Bergonie, Bordeaux; Antoine Adenis, Centre Oscar Lambret, Lille; Florence Duffaud, Hôpital de La Timone, Aix-Marseille Université, Marseille; Jean-Yves Blay, Centre Leon Berard, Lyon, France; Andres Poveda Velasco, Instituto Valenciano de Oncologia, Valencia; Javier M. Broto, Hospital Universitari Son Espases, Palma de Mallorca, Spain; Dusan Kotasek, Adelaide Cancer Centre, Kurralta Park, and University of Adelaide, Adelaide, South Australia; David Goldstein, Prince of Wales Hospital, New South Wales, Sydney; John R. Zalcberg, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia; Piotr Rutkowski, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland; Peter Hohenberger, Mannheim University Medical Center, Mannheim; Jörg T. Hartmann, Christian-Albrechts University, Kiel, Germany; Ian R. Judson, Royal Marsden Hospital; Winette T.A. van der Graaf, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, United Kingdom; Hans Gelderblom, Leiden University Medical Center, Leiden; Winette T.A. van der Graaf, Radboud University Medical Center, Nijmegen, the Netherlands; Saskia Litière, and Sandrine Marréaud, European Organisation for Research and Treatment of Cancer, Brussels, Belgium. paolo.casali@istitutotumori.mi.it. 2. Paolo G. Casali, Elena Fumagalli, and Alessandro Gronchi, Fondazione Istituto di Recovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milano; Angelo P. Dei Tos, Azienda Unità Locale Socio Sanitaria 9 Treviso, Treviso, Italy; Axel Le Cesne, Gustave Roussy, Villejuif; Antoine Italiano, Institut Bergonie, Bordeaux; Antoine Adenis, Centre Oscar Lambret, Lille; Florence Duffaud, Hôpital de La Timone, Aix-Marseille Université, Marseille; Jean-Yves Blay, Centre Leon Berard, Lyon, France; Andres Poveda Velasco, Instituto Valenciano de Oncologia, Valencia; Javier M. Broto, Hospital Universitari Son Espases, Palma de Mallorca, Spain; Dusan Kotasek, Adelaide Cancer Centre, Kurralta Park, and University of Adelaide, Adelaide, South Australia; David Goldstein, Prince of Wales Hospital, New South Wales, Sydney; John R. Zalcberg, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia; Piotr Rutkowski, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland; Peter Hohenberger, Mannheim University Medical Center, Mannheim; Jörg T. Hartmann, Christian-Albrechts University, Kiel, Germany; Ian R. Judson, Royal Marsden Hospital; Winette T.A. van der Graaf, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, United Kingdom; Hans Gelderblom, Leiden University Medical Center, Leiden; Winette T.A. van der Graaf, Radboud University Medical Center, Nijmegen, the Netherlands; Saskia Litière, and Sandrine Marréaud, European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
Abstract
PURPOSE: In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery patients with localized, high- or intermediate-risk GI stromal tumor (GIST). PATIENTS AND METHODS: Patients were randomly assigned to 2 years of imatinib 400 mg daily or no further therapy after surgery. The primary end point was overall survival; relapse-free survival (RFS), relapse-free interval, and toxicity were secondary end points. In 2009, given the concurrent improvement in prognosis of patients with advanced GIST, we changed the primary end point to imatinib failure-free survival (IFFS), with agreement of the independent data monitoring committee. We report on a planned interim analysis. RESULTS: A total of 908 patients were randomly assigned between December 2004 and October 2008: 454 to imatinib and 454 to observation. Of these, 835 patients were eligible. With a median follow-up of 4.7 years, 5-year IFFS was 87% in the imatinib arm versus 84% in the control arm (hazard ratio, 0.79; 98.5% CI, 0.50 to 1.25; P = .21); RFS was 84% versus 66% at 3 years and 69% versus 63% at 5 years (log-rank P < .001); and 5-year overall survival was 100% versus 99%, respectively. Among 528 patients with high-risk GIST by local pathologist, 5-year IFFS was 79% versus 73%; among 336 centrally reviewed high-risk patients, it was 77% versus 73%, respectively. CONCLUSION: This study confirms that adjuvant imatinib has an overt impact on RFS. No significant difference in IFFS was observed, although in the high-risk subgroup there was a trend in favor of the adjuvant arm. IFFS was conceived as a potential end point in the adjuvant setting because it is sensitive to secondary resistance, which is the main adverse prognostic factor in patients with advanced GIST.
RCT Entities:
PURPOSE: In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery patients with localized, high- or intermediate-risk GI stromal tumor (GIST). PATIENTS AND METHODS: Patients were randomly assigned to 2 years of imatinib 400 mg daily or no further therapy after surgery. The primary end point was overall survival; relapse-free survival (RFS), relapse-free interval, and toxicity were secondary end points. In 2009, given the concurrent improvement in prognosis of patients with advanced GIST, we changed the primary end point to imatinib failure-free survival (IFFS), with agreement of the independent data monitoring committee. We report on a planned interim analysis. RESULTS: A total of 908 patients were randomly assigned between December 2004 and October 2008: 454 to imatinib and 454 to observation. Of these, 835 patients were eligible. With a median follow-up of 4.7 years, 5-year IFFS was 87% in the imatinib arm versus 84% in the control arm (hazard ratio, 0.79; 98.5% CI, 0.50 to 1.25; P = .21); RFS was 84% versus 66% at 3 years and 69% versus 63% at 5 years (log-rank P < .001); and 5-year overall survival was 100% versus 99%, respectively. Among 528 patients with high-risk GIST by local pathologist, 5-year IFFS was 79% versus 73%; among 336 centrally reviewed high-risk patients, it was 77% versus 73%, respectively. CONCLUSION: This study confirms that adjuvant imatinib has an overt impact on RFS. No significant difference in IFFS was observed, although in the high-risk subgroup there was a trend in favor of the adjuvant arm. IFFS was conceived as a potential end point in the adjuvant setting because it is sensitive to secondary resistance, which is the main adverse prognostic factor in patients with advanced GIST.
Authors: Mark Fairweather; Vinod P Balachandran; George Z Li; Monica M Bertagnolli; Cristina Antonescu; William Tap; Samuel Singer; Ronald P DeMatteo; Chandrajit P Raut Journal: Ann Surg Date: 2018-08 Impact factor: 12.969
Authors: Heikki Joensuu; Mikael Eriksson; Kirsten Sundby Hall; Annette Reichardt; Barbara Hermes; Jochen Schütte; Silke Cameron; Peter Hohenberger; Philipp J Jost; Salah-Eddin Al-Batran; Lars H Lindner; Sebastian Bauer; Eva Wardelmann; Bengt Nilsson; Raija Kallio; Panu Jaakkola; Jouni Junnila; Thor Alvegård; Peter Reichardt Journal: JAMA Oncol Date: 2020-08-01 Impact factor: 31.777
Authors: J Martin-Broto; V Martinez-Marín; C Serrano; N Hindi; J A López-Guerrero; R Ramos-Asensio; A Vallejo-Benítez; D Marcilla-Plaza; R González-Cámpora Journal: Clin Transl Oncol Date: 2016-12-09 Impact factor: 3.405