Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Department of Oncology, Skåne University Hospital and Lund University, Lund, Sweden.
JAMA Oncol. 2020 Aug 1;6(8):1241-1246. doi: 10.1001/jamaoncol.2020.2091.
Adjuvant imatinib is associated with improved recurrence-free survival (RFS) when administered after surgery to patients with operable gastrointestinal stromal tumor (GIST), but its influence on overall survival (OS) has remained uncertain.
To evaluate the effect of adjuvant imatinib on OS of patients who have a high estimated risk for GIST recurrence after macroscopically complete surgery.
DESIGN, SETTING, AND PARTICIPANTS: In this open-label, randomized (1:1), multicenter phase 3 clinical trial conducted in Finland, Germany, Norway, and Sweden, 400 patients who had undergone macroscopically complete surgery for GIST with a high estimated risk for recurrence according to the modified National Institutes of Health Consensus Criteria were enrolled between February 2004 and September 2008. Data for this follow-up analysis were analyzed from September to November, 2019.
Imatinib 400 mg/d administered orally for either 12 months or 36 months after surgery.
The primary end point was RFS; the secondary objectives included OS and treatment safety.
The intention-to-treat cohort consisted of 397 patients (12-month group, 199; 36-month group, 198; 201 men and 196 women; median [IQR] age, 62 (51-69) years and 60 (51-67) years, during a median follow-up time of 119 months after the date of randomization, 194 RFS events and 96 OS events were recorded in the intention-to-treat population. Five-year and 10-year RFS was 71.4% and 52.5%, respectively, in the 36-month group and 53.0% and 41.8% in the 12-month group (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87; P = .003). In the 36-month group, 5-year OS and 10-year OS rates were 92.0% and 79.0%, respectively, and in the 12-month group 85.5% and 65.3% (HR, 0.55; 95% CI, 0.37-0.83; P = .004). The results were similar in the efficacy population, from which 15 patients who did not have GIST in central pathology review and 24 patients who had intra-abdominal metastases removed at surgery were excluded (36-month group, 10-year OS 81.6%; 12-month group, 66.8%; HR, 0.50; 95% CI, 0.32-0.80; P = .003). No new safety signals were detected.
Three years of adjuvant imatinib is superior in efficacy compared with 1 year of imatinib. Approximately 50% of deaths may be avoided during the first 10 years of follow-up after surgery with longer adjuvant imatinib treatment.
ClinicalTrials.gov Identifier: NCT00116935.
辅助伊马替尼在手术后用于可手术胃肠道间质瘤（GIST）患者时，与改善无复发生存（RFS）有关，但它对总生存（OS）的影响仍不确定。
评估辅助伊马替尼对高估计复发风险的 GIST 患者手术后 OS 的影响。
设计、地点和参与者：这是一项在芬兰、德国、挪威和瑞典进行的开放性、随机（1:1）、多中心的 3 期临床试验，纳入了 400 名根据改良国家卫生研究院共识标准具有高估计复发风险的 GIST 患者，这些患者在接受手术治疗后进行了宏观完全手术。这项随访分析的数据于 2019 年 9 月至 11 月进行了分析。
手术后口服伊马替尼 400 mg/d，持续 12 个月或 36 个月。
主要终点为 RFS；次要终点包括 OS 和治疗安全性。
意向治疗队列包括 397 名患者（12 个月组 199 例，36 个月组 198 例；201 名男性和 196 名女性；中位[IQR]年龄分别为 62[51-69]岁和 60[51-67]岁，在随机日期后的中位随访时间为 119 个月，意向治疗人群中记录了 194 例 RFS 事件和 96 例 OS 事件。36 个月组的 5 年和 10 年 RFS 分别为 71.4%和 52.5%，12 个月组分别为 53.0%和 41.8%（HR，0.66；95%CI，0.49-0.87；P = 0.003）。36 个月组的 5 年 OS 和 10 年 OS 率分别为 92.0%和 79.0%，12 个月组分别为 85.5%和 65.3%（HR，0.55；95%CI，0.37-0.83；P = 0.004）。排除了 15 名在中心病理检查中未发现 GIST 的患者和 24 名在手术中切除的腹腔内转移患者后，疗效人群的结果相似（36 个月组的 10 年 OS 率为 81.6%；12 个月组为 66.8%；HR，0.50；95%CI，0.32-0.80；P = 0.003）。未发现新的安全信号。
与 1 年的伊马替尼相比，3 年的辅助伊马替尼在疗效上更优。在手术后的前 10 年随访期间，使用更长时间的辅助伊马替尼治疗可能会避免约 50%的死亡。
ClinicalTrials.gov 标识符：NCT00116935。
