尼沃卢马布在患有转移性割抵抗性前列腺癌的患者中,有或没有DNA修复缺陷
Pedro Isaacsson Velho1,2, Diogo Assed Bastos3, Pedro Tofani Saint'ana1
1Hospital Moinhos de Vento, Porto Alegre, Brazil.
概括
基因修复缺陷 (DRD) 不能预测转移性割抵抗性前列腺癌 (mCRPC) 对nivolumab的反应. 需要进一步的研究来确定mCRPC患者免疫检查点抑制剂 (ICI) 治疗的生物标志物.
科学领域:
- 在瘤学瘤学.
- 生殖尿道癌症 生殖尿道癌症
- 癌症免疫学 癌症免疫学
背景情况:
- 免疫检查点抑制剂 (ICI) 在转移性割抵抗性前列腺癌 (mCRPC) 中显示出有限的疗效.
- 假设DNA修复缺陷 (DRD) 增加了新抗原负载,并预测了对ICI的反应.
- 确定mCRPC患者的预测生物标志物对于优化ICI治疗至关重要.
研究的目的:
- 研究DNA修复缺陷 (DRD) 作为mCRPC患者对nivolumab反应的预测生物标志物的潜力.
- 评估nivolumab在mCRPC患者中具有或没有DRD的临床活性.
主要方法:
- 一项II期,多中心,单臂试验在mCRPC患者中进行,这些患者先前接受过多塞塔克塞尔治疗.
- 通过循环瘤DNA (ctDNA) 和全外因子测序来评估DNA修复缺陷 (DRD).
- 主要终点是前列腺特异性抗原 (PSA) 50%的响应;次要终点包括客观响应率,无进展生存率和整体生存率.
主要成果:
- 在30.5%的患者中通过ctDNA和/或全外因子测序确定了DRD.
- 总体PSA50应答率为10.5%. 这是一个很好的结果.
- 在DRD和没有DRD的患者之间,没有观察到PSA50响应,客观响应率或无进展生存率的显著差异.
结论:
- 尼沃卢马布在mCRPC患者的一个子集中表现出临床活性,但DRD似乎不是一个预测性生物标志物.
- 需要新的生物标志物来识别最有可能从ICI治疗中受益的mCRPC患者.
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