TY - JOUR
T1 - Time to definitive failure to the first tyrosine kinase inhibitor in localized GI stromal tumors treated with imatinib as an adjuvant
T2 - A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup Randomized Trial in collaboration with the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas
AU - Casali, Paolo G.
AU - Le Cesne, Axel
AU - Velasco, Andres Poveda
AU - Kotasek, Dusan
AU - Rutkowski, Piotr
AU - Hohenberger, Peter
AU - Fumagalli, Elena
AU - Judson, Ian R.
AU - Italiano, Antoine
AU - Gelderblom, Hans
AU - Adenis, Antoine
AU - Hartmann, Jörg T.
AU - Duffaud, Florence
AU - Goldstein, David
AU - Broto, Javier M.
AU - Gronchi, Alessandro
AU - Dei Tos, Angelo P.
AU - Marréaud, Sandrine
AU - Van Der Graaf, Winette T.A.
AU - Zalcberg, John R.
AU - Litière, Saskia
AU - Blay, Jean Yves
N1 - Funding Information: Supported by the European Organisation for Research and Treatment of Cancer Charitable Trust and by an educational grant from Novartis, which also provided the study drug. We thank Anne Kirkpatrick, Axelle Nzokirantevye, Christine Olungu, Monia Ouali, Martine Van Glabbeke, and the other staff at European Organisation for Research and Treatment of Cancer headquarters who contributed to the success of the trial. We are grateful to all the patients who took part and their relatives and thank the participating investigators and centers.
Publisher Copyright:
© 2015 by American Society of Clinical Oncology.
Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2015/12/20
Y1 - 2015/12/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84955571000&partnerID=8YFLogxK
U2 - 10.1200/JCO.2015.62.4304
DO - 10.1200/JCO.2015.62.4304
M3 - Article
C2 - 26573069
AN - SCOPUS:84955571000
SN - 0732-183X
VL - 33
SP - 4276
EP - 4283
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 36
ER -
