辅助伊马替尼治疗可切除胃肠道间质瘤：一项随机试验，一年与三年的对比。

One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial.

机构信息

Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, PO Box 180, FIN-00029 Helsinki, Finland.

出版信息

JAMA. 2012 Mar 28;307(12):1265-72. doi: 10.1001/jama.2012.347.

DOI:10.1001/jama.2012.347

PMID:22453568

Abstract

CONTEXT

Adjuvant imatinib administered for 12 months after surgery has improved recurrence-free survival (RFS) of patients with operable gastrointestinal stromal tumor (GIST) compared with placebo.

OBJECTIVE

To investigate the role of imatinib administration duration as adjuvant treatment of patients who have a high estimated risk for GIST recurrence after surgery.

DESIGN, SETTING, AND PATIENTS: Patients with KIT-positive GIST removed at surgery were entered between February 2004 and September 2008 to this randomized, open-label phase 3 study conducted in 24 hospitals in Finland, Germany, Norway, and Sweden. The risk of GIST recurrence was estimated using the modified National Institutes of Health Consensus Criteria.

INTERVENTION

Imatinib, 400 mg per day, orally for either 12 months or 36 months, started within 12 weeks of surgery.

MAIN OUTCOME MEASURES

The primary end point was RFS; the secondary end points included overall survival and treatment safety.

RESULTS

Two hundred patients were allocated to each group. The median follow-up time after randomization was 54 months in December 2010. Diagnosis of GIST was confirmed in 382 of 397 patients (96%) in the intention-to-treat population at a central pathology review. KIT or PDGFRA mutation was detected in 333 of 366 tumors (91%) available for testing. Patients assigned for 36 months of imatinib had longer RFS compared with those assigned for 12 months (hazard ratio [HR], 0.46; 95% CI, 0.32-0.65; P < .001; 5-year RFS, 65.6% vs 47.9%, respectively) and longer overall survival (HR, 0.45; 95% CI, 0.22-0.89; P = .02; 5-year survival, 92.0% vs 81.7%). Imatinib was generally well tolerated, but 12.6% and 25.8% of patients assigned to the 12- and 36-month groups, respectively, discontinued imatinib for a reason other than GIST recurrence.

CONCLUSION

Compared with 12 months of adjuvant imatinib, 36 months of imatinib improved RFS and overall survival of GIST patients with a high risk of GIST recurrence.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00116935.

摘要

背景

与安慰剂相比，手术后接受 12 个月辅助伊马替尼治疗可改善可切除胃肠道间质瘤（GIST）患者的无复发生存率（RFS）。

目的

研究伊马替尼给药时间作为辅助治疗手术后 GIST 复发风险高的患者的作用。

设计、地点和患者：2004 年 2 月至 2008 年 9 月期间，在芬兰、德国、挪威和瑞典的 24 家医院进行了这项随机、开放标签的 3 期研究，入组了手术切除的 KIT 阳性 GIST 患者。GIST 复发风险使用改良的美国国立卫生研究院共识标准进行评估。

干预措施

手术后 12 周内开始每天口服 400mg 伊马替尼，持续 12 个月或 36 个月。

主要终点

RFS；次要终点包括总生存和治疗安全性。

结果

200 名患者被随机分配到每个组。2010 年 12 月，在中央病理审查中，意向治疗人群的中位随访时间为随机分组后 54 个月。在可用于检测的 366 个肿瘤中，382 个（96%）在中心病理学复查中确诊为 GIST。在 333 个可检测的肿瘤中，检测到 KIT 或 PDGFRA 突变。与接受 12 个月伊马替尼治疗的患者相比，接受 36 个月伊马替尼治疗的患者 RFS 更长（风险比[HR]，0.46；95%CI，0.32-0.65；P<0.001；5 年 RFS，分别为 65.6%和 47.9%），总生存时间更长（HR，0.45；95%CI，0.22-0.89；P=0.02；5 年生存率分别为 92.0%和 81.7%）。伊马替尼总体耐受性良好，但分别有 12.6%和 25.8%的接受 12 个月和 36 个月伊马替尼治疗的患者因 GIST 以外的原因停止了伊马替尼治疗。