欧洲癌症研究与治疗组织软组织和骨肉瘤小组（STBSG）、澳大利亚胃肠道试验小组（AGITG）、UNICANCER、法国肉瘤小组（FSG）、意大利肉瘤小组（ISG）以及西班牙肉瘤研究小组（GEIS）关于伊马替尼作为局限性胃肠道间质瘤（GIST）辅助治疗的随机试验最终分析。
Final analysis of the randomized trial on imatinib as an adjuvant in localized gastrointestinal stromal tumors (GIST) from the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), the Australasian Gastro-Intestinal Trials Group (AGITG), UNICANCER, French Sarcoma Group (FSG), Italian Sarcoma Group (ISG), and Spanish Group for Research on Sarcomas (GEIS).
作者信息
Casali P G, Le Cesne A, Velasco A P, Kotasek D, Rutkowski P, Hohenberger P, Fumagalli E, Judson I R, Italiano A, Gelderblom H, Penel N, Hartmann J T, Duffaud F, Goldstein D, Martin-Broto J, Gronchi A, Wardelmann E, Marréaud S, Zalcberg J R, Litière S, Blay J-Y
机构信息
Fondazione IRCCS Istituto Nazionale Tumori, and University of Milan, Milano, Italy; Gustave Roussy, Villejuif, France.
Instituto Valenciano De Oncologia, Valencia, Spain.
出版信息
Ann Oncol. 2021 Apr;32(4):533-541. doi: 10.1016/j.annonc.2021.01.004. Epub 2021 Jan 19.
BACKGROUND
In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery in localized, high/intermediate-risk gastrointestinal stromal tumors (GIST) patients. Interim analysis results were published in 2015 upon recommendation from an independent data review committee. We report the final outcome of the study.
PATIENTS AND METHODS
This was a randomized, open-label, multicenter phase III trial carried out at 112 hospitals in 12 countries. Patients were randomized to 2 years of imatinib, 400 mg daily, or no further therapy after surgery. The primary endpoint was imatinib failure-free survival (IFFS), while relapse-free survival (RFS), relapse-free interval (RFI), overall survival (OS) and toxicity were secondary endpoints. Adjusting for the interim analyses, results on IFFS were assessed on a 4.3% significance level; for the other endpoints, 5% was used.
RESULTS
Nine hundred and eight patients were randomized between January 2005 and October 2008: 454 to imatinib and 454 to observation; 835 patients were eligible. With a median follow-up of 9.1 years, 5 (10)-year IFFS was 87% (75%) in the imatinib arm versus 83% (74%) in the control arm [hazard ratio (HR) = 0.87, 95.7% confidence interval (CI) (0.65; 1.15), P = 0.31]; RFS was 70% versus 63% at 5 years and 63% versus 61% at 10 years, [HR = 0.71, 95% CI (0.57; 0.89), P = 0.002]; OS was 93% versus 92% at 5 years and 80% versus 78% at 10 years [HR = 0.88, 95% CI (0.65; 1.21), P = 0.43]. Among 526 patients with high-risk GIST by local pathology, 10-year IFFS and RFS were 69% versus 61%, and 48% versus 43%, respectively.
CONCLUSIONS
With 9.1 years of follow-up, a trend toward better long-term IFFS in imatinib-treated patients was observed in the high-risk subgroup. Although the difference was not statistically significant and the surrogacy value of such an endpoint is not validated, this may be seen as supporting the results reported by the Scandinavian/German trial, showing a sustained small but significant long-term OS benefit in high-risk GIST patients treated with 3 years of adjuvant imatinib.
背景
2004年，我们启动了一项组间随机试验，比较局部高危/中危胃肠道间质瘤（GIST）患者在R0-R1手术后辅助使用伊马替尼与不再接受进一步治疗的效果。经独立数据审查委员会建议，于2015年公布了中期分析结果。我们报告该研究的最终结果。
患者与方法
这是一项在12个国家的112家医院开展的随机、开放标签、多中心III期试验。患者被随机分为接受2年每日400毫克伊马替尼治疗组或术后不再接受进一步治疗组。主要终点是伊马替尼无失败生存（IFFS），而无复发生存（RFS）、无复发间期（RFI）、总生存（OS）和毒性为次要终点。在调整中期分析后，对IFFS结果在4.3%的显著性水平上进行评估；对于其他终点，采用5%的显著性水平。
结果
2005年1月至2008年10月期间，908例患者被随机分组：454例接受伊马替尼治疗，454例接受观察；835例患者符合条件。中位随访9.1年，伊马替尼组5（10）年IFFS为87%（75%），对照组为83%（74%）[风险比（HR）=0.87，95.7%置信区间（CI）（0.65；1.15），P=0.31]；5年时RFS分别为70%和63%，10年时分别为63%和61%，[HR=0.71，95%CI（0.57；0.89），P=0.002]；5年时OS分别为93%和92%，10年时分别为80%和78%[HR=0.88，95%CI（0.65；1.21），P=0.43]。在526例经局部病理诊断为高危GIST的患者中，10年IFFS和RFS分别为69%和61%，以及48%和43%。
结论
经过9.1年的随访，在高危亚组中观察到接受伊马替尼治疗的患者长期IFFS有改善趋势。尽管差异无统计学意义且该终点的替代价值未得到验证，但这可被视为支持斯堪的纳维亚/德国试验报告的结果，即接受3年辅助伊马替尼治疗的高危GIST患者长期OS有持续的小但显著的获益。
Zotero 插件