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在状细胞肺癌中MAPK路径激活变化和免疫疗法的有效性:随机,前性SQUINT试验的结果

Federico Cappuzzo¹, Biagio Ricciuti^2,3, Angelo Delmonte⁴

¹Department of Medical Oncology 2, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy.

Clinical cancer research : an official journal of the American Association for Cancer Research

|January 21, 2025

概括

激活MAPK通路的改变预测了肺状细胞癌 (LSCC) 的更好的免疫疗法反应. 基因分析对于优化晚期LSCC患者治疗策略至关重要.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
基因组学就是基因组学.

背景情况:

免疫疗法在肺平细胞癌 (LSCC) 的疗效是可变的.
需要在LSCC中预测免疫治疗反应的预测生物标志物.

研究的目的:

评估nivolumab加 ipilimumab (NI) 与基于的化疗加nivolumab (N-CT) 在晚期或转移的LSCC的疗效.
确定生物标志物,特别是激活MAPK途径的改变,这些生物标志物可以预测LSCC的免疫治疗反应.

主要方法:

一个随机的II期试验 (SQUINT),比较化学前不经过治疗的LSCC患者的NI和N-CT.
分析MAPK通路的改变和免疫细胞透 (CD8+PD1+,FOXP3+) 作为潜在的生物标志物.
验证队列分析,以证实免疫治疗先验患者的发现.

主要成果:

患有MAPK通路激活变化的患者对免疫治疗的反应率较高 (43%对15%).
MAPK的改变与明显更长的无进展生存期 (P=0.03) 和整体生存期 (P<0.001) 相关.
在MAPK改变的瘤中观察到CD8+PD1+T细胞增加和CD8+PD1+/FOXP3比率更高.

结论:

激活MAPK通路的改变是LSCC免疫疗法疗效的新型预测生物标志物.
基因分析,特别是对MAPK途径的改变,对于指导LSCC治疗决策具有临床意义.
这些发现强调了分子分析在个性化癌症治疗中的重要性.

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