在子宫内膜癌中使用莱特醇,阿贝马西克利布和美特福明:非随机的第二阶段试验
Panagiotis A Konstantinopoulos1, Ningxuan Zhou2, Richard T Penson3
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. Panagiotis_konstantinopoulos@dfci.harvard.edu.
Nature communications
|December 3, 2025
概括
这项研究研究了子宫内膜癌 (EC) 的组合疗法,发现32%的客观反应率和6个月后69.8%的无进展生存率. 某些突变与治疗效益相关.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 遗传学 是一个遗传学.
背景情况:
- 临床前研究表明,雌激素受体 (ER),CDK4/6和PI3K通路抑制之间的协同作用.
- 甲福明在子宫内膜癌 (EC) 中表现出PI3K/mTOR信号抑制.
研究的目的:
- 评估包括莱特醇,阿贝马西克利布和甲胺在内的组合疗法的疗效和安全性,用于ER阳性子宫内膜异位体EC.
- 确定客观反应率 (ORR) 和6个月无进展生存率 (PFS6) 作为主要终点.
主要方法:
- 一项非随机的第二阶段研究 (NCT03675893) 涉及25名ER阳性子宫内膜体EC患者.
- 患者接受了莱特醇 (每天2.5毫克),阿贝马西克利布 (每天两次150毫克) 和甲胺 (每天500毫克).
- 评估ORR,PFS6,整体存活率,反应持续时间和毒性. 进行了药理动力学分析.
主要成果:
- ORR为32% (3个完全响应,5个部分响应).
- 估计PFS6为69.8%,PFS的中位数为19.4个月.
- 没有因毒性而停止治疗;CTNNB1突变与临床益处相关. 随着同时使用,甲胺的暴露增加了>3倍.
结论:
- 莱特醇,阿贝马西克利布和美特福林的组合显示出对ER阳性子宫内膜体EC的有希望的活性.
- 瘤分子分析,特别是CTNNB1突变,可以预测对这种疗法的反应.
- 这种组合耐受性很好,并增强了对美特福林的暴露.
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