Introduction: While the efficacy of immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC) patients with actionable genetic alterations (AGAs) is modest, certain patients demonstrate improved survival. Thus, this study aimed to evaluate the benefits of ICIs in NSCLC patients with diverse AGAs and verify the predictive biomarkers of ICI efficacy. Methods: From January 2018 to July 2022, this study compared the progression-free survival (PFS) of NSCLC patients with different AGAs treated with ICI monotherapy as second- or later-line therapy at Samsung Medical Center. To ascertain the predictors of ICIs efficacy, we adjusted ICIs’ effects on PFS in terms of clinical and molecular biomarkers. Results:EGFR(46.0%) was the most prevalent mutation in 324 patients. In multivariate analysis, PD-L1 positivity (tumor proportion score (TPS) ≥ 1%) (HR = 0.41) and the use of steroids for immune-related adverse events (HR = 0.46) were positive factors for ICI therapy in the AGAs group. Co-existing mutation ofSTK11withKRASmutation (HR = 4.53) andTP53withMETmutation (HR = 9.78) was negatively associated with survival. Conclusions: The efficacy of ICI treatment varied across AGA subtypes, but patients withKRAS,MET, andBRAFmutations demonstrated relatively long-duration benefits of ICI therapy. PD-L1 was a significant positive predictive biomarker in all AGA groups.
引言：尽管免疫检查点抑制剂（ICIs）在治疗携带可操作基因改变（AGAs）的非小细胞肺癌（NSCLC）患者中疗效有限，但部分患者仍显示出生存获益。因此，本研究旨在评估ICIs在不同AGAs的NSCLC患者中的疗效，并验证ICIs疗效的预测性生物标志物。方法：本研究于2018年1月至2022年7月期间，在三星医疗中心比较了接受ICIs单药作为二线或后线治疗、携带不同AGAs的NSCLC患者的无进展生存期（PFS）。为确定ICIs疗效的预测因素，我们根据临床和分子生物标志物调整了ICIs对PFS的影响。结果：在324例患者中，EGFR突变最为常见（46.0%）。多变量分析显示，在AGAs组中，PD-L1阳性（肿瘤比例评分（TPS）≥1%）（HR=0.41）以及因免疫相关不良事件使用类固醇（HR=0.46）是ICIs治疗的积极因素。STK11与KRAS突变共存（HR=4.53）以及TP53与MET突变共存（HR=9.78）与生存期呈负相关。结论：ICIs治疗的疗效因AGA亚型而异，但携带KRAS、MET和BRAF突变的患者显示出相对持久的ICIs治疗获益。PD-L1在所有AGA组中均为显著的阳性预测生物标志物。
肿瘤(癌症)患者之家