不小细胞肺癌的一天时间免疫化疗:一个随机的第三期试验
Zhe Huang1,2, Liang Zeng1, Zhaohui Ruan1,3
1Early Phase Clinical Trial Center, Department of Investigational Cancer Therapeutics, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Nature medicine
|February 2, 2026
概括
一天的早期时间 (ToD) 免疫化疗显著改善非小细胞肺癌 (NSCLC) 患者的无进展生存期 (PFS) 和整体生存期 (OS). 这种方法与晚期的ToD治疗相比,增强了抗瘤CD8+T细胞活性.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 时间生物学 时间生物学
背景情况:
- 回顾性研究表明,一天中的时间 (ToD) 影响免疫化学疗法的疗效.
- 未来的验证对于癌症早期的ToD治疗策略至关重要.
研究的目的:
- 为了评估早期与晚期ToD对抗PD-1药物的有效性和安全性,在未经治疗的NSCLC患者中.
- 评估 ToD 对患者存活率和免疫细胞特征的影响.
主要方法:
- 一个随机的第三期试验 (LungTIME-C01) 涉及210名缺乏驱动突变的NSCLC患者.
- 在抗PD-1治疗的前四个周期中,患者被分配到早期 (在15:00之前) 或晚期 (在15:00之后) 的ToD.
- 主要终点:无进展生存 (PFS);次要终点:整体生存 (OS),客观反应率 (ORR) 和免疫细胞分析.
主要成果:
- 早期ToD治疗显著改善了PFS中位数 (11.3个月与5.7个月;HR 0.40) 和OS中位数 (28.0个月与16.8个月;HR 0.42).
- 在早期的ToD组中观察到,早晨CD8+ T细胞增加和激活到耗尽的CD8+ T细胞的比例更高.
- 两组之间不良事件的概况是相似的,没有新的安全问题.
结论:
- 一天中的早期免疫化学疗法在NSCLC中显示出实质性的临床益处,改善了PFS和OS.
- 观察到抗瘤CD8+T细胞特征的增强支持早期ToD治疗的有效性.
- 这项研究提供了强有力的证据,支持将慢性疗法纳入NSCLC治疗方案.
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