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对Olaparib和ATR抑制剂Ceralasertib进行的多中心II期研究,用于转移性结抵抗性前列腺癌 (TRAP) 的治疗

Irene Tsung¹, David C Smith¹, Elisabeth I Heath²

¹Department of Internal Medicine, Division of Hematology and Oncology, Rogel Cancer Center, University of Michigan, Ann Arbor, MI.

JCO precision oncology

|September 16, 2025

概括

奥拉巴里布和塞拉拉塞尔蒂布的组合在具有同源重组能力的转移性割抵抗性前列腺癌 (mCRPC) 的患者中显示出有限的疗效. 在HRRm患者中,应答率并没有超过单剂PARP抑制剂患者的应答率.

科学领域:

在瘤学瘤学.
临床试验临床试验
前列腺癌研究研究前列腺癌

背景情况:

临床前的数据表明,聚基糖酶 (PARP) 抑制剂olaparib与突变性telangiectasia和Rad3相关的 (ATR) 抑制剂ceralasertib之间的协同抗瘤作用.
这种组合疗法在转移性割抵抗性前列腺癌 (mCRPC) 患者中被探索其潜在益处.

研究的目的:

评估在mCRPC患者中结合olaparib和ceralasertib的疗效.
评估同源复合精通 (HRP) 和同源复合修复基因突变 (HRRm) 亚组中的治疗结果.

主要方法:

一项临床试验招募了35名HRP和12名HRRm PARP抑制剂先验mCRPC患者.
患者在28天的周期中接受了olaparib和ceralasertib.
疾病应答率 (dRR) 是HRP患者的主要终点;二级终点包括HRRm患者的dRR,无进展生存 (PFS) 和安全.

主要成果:

在HRP患者中观察到11%的疾病应答率 (dRR) (4/35).
在12名HRRm患者中,有4名患者也有反应.
HRP患者的PFS中位数为8.2个月,其中36%的人患有3级或更高毒性,主要是贫血.

结论:

塞拉拉塞尔蒂布和奥拉帕里布的组合在HRP mCRPC群体中表现出有限的活性.
HRRm患者的应答率没有超过使用单剂PARP抑制剂的先前研究的应答率.

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