Ten-Year Progression-Free and Overall Survival in Patients With Unresectable or Metastatic GI Stromal Tumors: Long-Term Analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group Intergroup Phase III Randomized Trial on Imatinib at Two Dose Levels

被引:154
作者
Casali, Paolo G. [1 ,2 ]
Zalcberg, John [3 ]
Le Cesne, Axel [6 ]
Reichardt, Peter [9 ]
Blay, Jean-Yves [7 ]
Lindner, Lars H. [10 ]
Judson, Ian R. [12 ]
Schoffski, Patrick [13 ]
Leyvraz, Serge [15 ]
Italiano, Antoine [8 ]
Grunwald, Viktor [11 ]
Pousa, Antonio Lopez [16 ]
Kotasek, Dusan [4 ,5 ]
Sleijfer, Stefan [17 ]
Kerst, Jan M. [18 ]
Rutkowski, Piotr [21 ,22 ]
Fumagalli, Elena [1 ]
Hogendoorn, Pancras [19 ]
Litiere, Saskia [14 ]
Marreaud, Sandrine [14 ]
van der Graaf, Winette [12 ,20 ]
Gronchi, Alessandro [1 ]
Verweij, Jaap [17 ]
机构
[1] Fdn Ist Ricovero & Cura Carattere Sci, Ist Nazl Tumori, Via Venezian 1, I-20133 Milan, Italy
[2] Univ Milan, Milan, Italy
[3] Peter MacCallum Canc Inst, East Melbourne, Vic, Australia
[4] Adelaide Canc Ctr, Kurralta Pk, Adelaide, SA, Australia
[5] Univ Adelaide, Adelaide, SA, Australia
[6] Gustave Roussy, Villejuif, France
[7] Ctr Leon Berard, NetSARC & Site Rech Integree Canc Lyon, Lyon, France
[8] Inst Bergonie, Bordeaux, France
[9] HELIOS Klinikum Berlin Buch, Berlin, Germany
[10] Klinikum Univ Munchen, Munich, Germany
[11] Sch Hannover, Hannover, Germany
[12] Royal Marsden Hosp, London, England
[13] Univ Ziekenhuizen Leuven, Campus Gasthuisberg, Leuven, Belgium
[14] European Org Res & Treatment Canc Headquarters, Brussels, Belgium
[15] Univ Hosp, Lausanne, Switzerland
[16] Hosp Santa Creu I Sant Pau, Barcelona, Spain
[17] Erasmus Univ, Med Ctr, Erasmus MC Canc Inst, Rotterdam, Netherlands
[18] Netherlands Canc Inst, Amsterdam, Netherlands
[19] Leiden Univ, Med Ctr, Leiden, Netherlands
[20] Radboud Univ Nijmegen, Med Ctr Nijmegen, Nijmegen, Netherlands
[21] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland
[22] Inst Oncol, Warsaw, Poland
关键词
TYROSINE KINASE; MESYLATE; EFFICACY; SAFETY; KIT; INHIBITOR; MUTATIONS;
D O I
10.1200/JCO.2016.71.0228
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PurposeTo report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs).Patients and MethodsEligible patients with advanced CD117-positive GIST from 56 institutions in 13 countries were randomly assigned to receive either imatinib 400 mg or 800 mg daily. Patients on the 400-mg arm were allowed to cross over to 800 mg upon progression.ResultsBetween February 2001 and February 2002, 946 patients were accrued. Median age was 60 years (range, 18 to 91 years). Median follow-up time was 10.9 years. Median progression-free survival times were 1.7 and 2.0 years in the 400- and 800-mg arms, respectively (hazard ratio, 0.91; P = .18), and median overall survival time was 3.9 years in both treatment arms. The estimated 10-year progression-free survival rates were 9.5% and 9.2% for the 400- and 800-mg arms, respectively, and the estimated 10-year overall survival rates were 19.4% and 21.5%, respectively. At multivariable analysis, age (< 60 years), performance status (0 v 1), size of the largest lesion (smaller), and KIT mutation (exon 11) were significant prognostic factors for the probability of surviving beyond 10 years.ConclusionThis trial was carried out on a worldwide intergroup basis, at the beginning of the learning curve of the use of imatinib, in a large population of patients with advanced GIST. With a long follow-up, 6% of patients are long-term progression free and 13% are survivors. Among clinical prognostic factors, only performance status, KIT mutation, and size of largest lesion predicted long-term outcome, likely pointing to a lower burden of disease. Genomic and/or immune profiling could help understand long-term survivorship. Addressing secondary resistance remains a therapeutic challenge.
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收藏
页码:1713 / +
页数:11
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