文章：

接受帕博利珠单抗治疗的非小细胞肺癌患者中免疫相关不良事件、全身炎症生物标志物与生存结局的关联研究

Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer

原文发布日期：21 November 2023

DOI: 10.3390/cancers15235502

类型: Article

开放获取: 是

英文摘要：

Background: Pembrolizumab monotherapy for non-small-cell lung cancer (NSCLC) expressing PD-L1 ≥ 50% doubles five-year survival rates compared to chemotherapy. However, immune-related adverse events (irAEs) can cause severe, long-term toxicity necessitating high-dose steroids and/or treatment cessation. Interestingly, patients experiencing irAEs demonstrate better survival outcomes. Biomarkers of systemic inflammation, including the Scottish Inflammatory Prognostic Score (SIPS), also predict survival in this patient group. This study examines the relationship between inflammatory status, irAEs, and survival outcomes in NSCLC. Methods: A retrospective analysis was conducted on patients with NSCLC expressing PD-L1 ≥ 50% receiving first-line pembrolizumab monotherapy at a large cancer centre in Scotland. Regression analyses were conducted to examine the relationship between SIPS, irAEs, and survival. Results: 83/262 eligible patients (32%) experienced an irAE. Dermatological, endocrine, gastrointestinal, and hepatic, but not pulmonary, irAEs were associated with prolonged PFS and OS (p<= 0.011). Mild irAEs were associated with better PFS and OS in all patients, including on time-dependent analyses (HR0.61 [95% CI 0.41–0.90],p= 0.014 and HR0.41 [95% CI 0.26–0.63],p< 0.001, respectively). SIPS predicted PFS (HR 1.60 [95% CI 1.34–1.90],p< 0.001) and OS (HR 1.69 [95% CI 1.41–2.02],p< 0.001). SIPS predicted the occurrence of any irAE in all patients (p= 0.011), but not on 24-week landmark analyses (p= 0.174). The occurrence of irAEs predicted favourable outcomes regardless of the baseline inflammatory status (p= 0.015). Conclusion: The occurrence of certain irAEs is associated with a survival benefit in patients with NSCLC expressing PD-L1 ≥ 50% receiving pembrolizumab. We find that the association between low levels of systemic inflammation and the risk of irAEs is confounded by their independent prognostic value.

摘要翻译： 

背景：对于程序性死亡配体1（PD-L1）表达≥50%的非小细胞肺癌（NSCLC）患者，帕博利珠单抗单药治疗相较于化疗可将五年生存率提高一倍。然而，免疫相关不良事件（irAEs）可能导致严重且长期的毒性反应，需要大剂量类固醇治疗和/或中止治疗。值得注意的是，发生irAEs的患者往往表现出更好的生存结局。系统性炎症生物标志物，包括苏格兰炎症预后评分（SIPS），也被证实可预测此类患者的生存情况。本研究旨在探讨NSCLC患者中炎症状态、irAEs与生存结局之间的关系。 方法：本研究对苏格兰一家大型癌症中心收治的、PD-L1表达≥50%并接受一线帕博利珠单抗单药治疗的NSCLC患者进行了回顾性分析。采用回归分析探究SIPS、irAEs与生存之间的关系。 结果：在262例符合条件的患者中，83例（32%）发生了irAE。皮肤、内分泌、胃肠道和肝脏的irAEs（不包括肺部irAE）与更长的无进展生存期（PFS）和总生存期（OS）相关（p≤0.011）。在所有患者中，轻度irAEs与更好的PFS和OS相关，包括在时间依赖性分析中（风险比[HR]分别为0.61 [95% CI 0.41–0.90]，p=0.014和0.41 [95% CI 0.26–0.63]，p<0.001）。SIPS可预测PFS（HR 1.60 [95% CI 1.34–1.90]，p<0.001）和OS（HR 1.69 [95% CI 1.41–2.02]，p<0.001）。SIPS可预测所有患者中任何irAE的发生（p=0.011），但在24周界标分析中则无此预测作用（p=0.174）。无论基线炎症状态如何，irAEs的发生均预示着更佳的结局（p=0.015）。 结论：在接受帕博利珠单抗治疗的PD-L1表达≥50%的NSCLC患者中，特定irAEs的发生与生存获益相关。我们发现，低水平系统性炎症与irAEs风险之间的关联，因其独立的预后价值而变得复杂。

原文链接：

Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer