Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany.
Clin Cancer Res. 2023 Sep 1;29(17):3313-3319. doi: 10.1158/1078-0432.CCR-22-3980.
Limited data are available about the influence of KIT and PDGFRA mutations on overall survival (OS) of patients with gastrointestinal stromal tumor (GIST) treated with adjuvant imatinib.
The Scandinavian Sarcoma Group XVIII/AIO multicenter trial accrued 400 patients with a high risk for GIST recurrence after macroscopically complete surgery between February 4, 2004, and September 29, 2008. The patients received adjuvant imatinib 400 mg/day for either 1 year or 3 years based on random allocation. We analyzed using conventional sequencing KIT and PDGFRA mutations centrally from 341 (85%) patients who had localized, centrally confirmed GIST, and correlated the results with recurrence-free survival (RFS) and OS in exploratory analyses.
During a median follow-up time of 10 years, 164 RFS events and 76 deaths occurred. Most patients were re-treated with imatinib when GIST recurred. Patients with KIT exon 11 deletion or indel mutation treated with 3 years of adjuvant imatinib survived longer than patients treated for 1 year [10-year OS 86% versus 64%, respectively; HR, 0.34; 95% confidence interval (CI), 0.15-0.72; P = 0.007], and also had longer RFS (10-year RFS 47% versus 29%; HR, 0.48; 95% CI, 0.31-0.74; P < 0.001). Patients with KIT exon 9 mutation had unfavorable OS regardless of the duration of adjuvant imatinib.
Compared with 1 year of imatinib, 3 years of adjuvant imatinib led to 66% reduction in the estimated risk of death and a high 10-year OS rate in the subset of patients with a KIT exon 11 deletion/indel mutation.
关于 KIT 和 PDGFRA 突变对接受辅助伊马替尼治疗的胃肠道间质瘤（GIST）患者总生存（OS）的影响，目前仅有有限的数据。
斯堪的纳维亚肉瘤组 XVIII/AIO 多中心试验纳入了 400 例在 2004 年 2 月 4 日至 2008 年 9 月 29 日之间接受了大体完全手术后复发风险高的 GIST 患者。这些患者根据随机分配接受辅助伊马替尼 400mg/天，持续 1 年或 3 年。我们使用常规测序分析了 341 例（85%）局限性、中心确认的 GIST 患者的 KIT 和 PDGFRA 突变，并在探索性分析中分析了这些结果与无复发生存（RFS）和 OS 的相关性。
在中位随访 10 年期间，发生了 164 例 RFS 事件和 76 例死亡。大多数患者在 GIST 复发时接受了再次伊马替尼治疗。接受 3 年辅助伊马替尼治疗的 KIT 外显子 11 缺失或插入突变患者的生存时间长于接受 1 年治疗的患者[10 年 OS 分别为 86%和 64%；HR，0.34；95%置信区间（CI），0.15-0.72；P=0.007]，并且 RFS 也更长[10 年 RFS 分别为 47%和 29%；HR，0.48；95%CI，0.31-0.74；P<0.001]。无论辅助伊马替尼的持续时间如何，KIT 外显子 9 突变患者的 OS 均较差。
与 1 年伊马替尼相比，3 年辅助伊马替尼可使 KIT 外显子 11 缺失/插入突变患者的死亡风险估计降低 66%，并使 10 年 OS 率显著提高。
