在直肠癌中进行双免疫检查点抑制加上新辅助化疗:一项随机临床试验
Johannes Laengle1, Irene Kuehrer1, Askin Kulu1
1Division of Visceral Surgery, Department of General Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
JAMA network open
|August 22, 2025
概括
添加伊皮利穆马布和尼沃卢马布用于直肠癌的新辅助化疗是安全的和可行的. 这种组合虽然没有显著改善完整反应率,但在第二阶段试验中显示出有前途的临床活性.
科学领域:
- 癌症学
- 免疫疗法
- 胃肠道瘤学
背景情况:
- 微卫星稳定的直肠癌通常对免疫检查点抑制剂 (ICI) 具有抗药性.
- 放射治疗可以增强瘤免疫性,这表明将放射治疗与ICI结合起来可能有好处.
- 在新辅助性直肠癌治疗方案中,将CTLA-4抑制剂与PD-1抑制剂结合使用的附加益处需要进一步研究.
研究的目的:
- 评估结合伊皮利穆巴 (一种抗CTLA-4抗体) 和尼沃卢穆巴 (一种抗PD-1抗体) 与新辅助化疗 (CRT) 治疗直肠癌的安全性和可行性.
- 评估手术并发症和重复手术的发生率.
- 确定临床和病理反应率作为次要结果.
主要方法:
- 进行了一项前性,随机的,开放的,多中心的2期临床试验 (CHINOREC).
- 患者接受新辅助CRT (50Gy与capecitabine) 单独或与依次性ipilimumab和nivolumab.
- 在CRT治疗后10~12周进行了手术切除,并进行了治疗意向分析.
主要成果:
- 与单独使用CRT相比,CRT与伊皮利穆巴和尼沃卢马布的联合治疗是安全的和可行的,而手术并发症或重新手术的发生率没有显著增加.
- 在这两组中,手术并发症率为77% (任何级别).
- 在两组中,主要病理反应和完整反应率都很高,两组之间没有显著差异.
结论:
- 在不增加手术并发症的情况下,将伊皮利马布和尼沃马布整合到新辅助性直肠癌CRT中是安全的和可行的.
- 双重ICI疗法显示出有前途的临床活性,尽管完全响应率没有显著改善.
- 需要进一步研究以优化治疗策略,包括联合放射治疗和ICI治疗的时间,剂量和患者选择.
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