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当前免疫检查点抑制剂在非小细胞肺癌中的安全性。

Safety of current immune checkpoint inhibitors in non-small cell lung cancer.

机构信息

Department of Cancer Medicine, Thoracic Oncology Unit, Gustave Roussy Cancer Campus, Villejuif, France.

出版信息

Expert Opin Drug Saf. 2021 Jun;20(6):651-667. doi: 10.1080/14740338.2021.1867100. Epub 2021 Mar 25.

DOI:10.1080/14740338.2021.1867100
PMID:33393387
Abstract

: Immune checkpoint inhibitors (ICIs) achieved response rates around 20% in advanced non-small cell lung cancer (NSCLC) with 8% of patients becoming long-term survivors. Outcomes have improved with the addition of chemotherapy to immunotherapy or the combination of anti-PD(L)1 with anti-CTLA-4 agents.: The incidence of immune-related adverse events (irAEs) in patients with NSCLC treated with ICIs varied across clinical trials and real-life studies. The onset of irAEs was 10 weeks. Toxic deaths from irAEs following anti-PD(L)1 administration resulted mainly from pneumonitis. Some irAEs such as rash and thyroiditis were probably associated with better clinical outcomes, though confounding biases exist. Investigations are on-going to determine ideal biomarkers to predict the occurrence, to screen for and to diagnose irAEs.: Prevention, anticipation, detection, treatment and careful monitoring are the five principles that characterize our management of irAEs. Distinguishing immune-induced pneumonitis from progression, pseudo progression, hyper progression, or other etiologies (COVID-19) can be particularly challenging in lung cancer due to the baseline vulnerable pulmonary function and thus requires caution and teamwork. We treat patients according to institutional and international guidelines and we only rechallenge them with ICIs after resolution of the AE and corticosteroid tapering.

摘要

免疫检查点抑制剂 (ICIs) 在晚期非小细胞肺癌 (NSCLC) 中的反应率约为 20%,其中 8%的患者成为长期幸存者。随着化疗联合免疫治疗或抗 PD(L)1 与抗 CTLA-4 药物联合应用,其疗效得到了改善。

在接受 ICI 治疗的 NSCLC 患者中,免疫相关不良事件 (irAE) 的发生率在临床试验和真实世界研究中存在差异。irAE 的发病时间为 10 周。抗 PD(L)1 治疗后 irAE 导致的毒性死亡主要来自于肺炎。虽然存在混杂偏倚,但某些 irAE(如皮疹和甲状腺炎)可能与更好的临床结局相关。目前正在进行研究以确定理想的生物标志物来预测、筛查和诊断 irAE。

预防、预期、检测、治疗和仔细监测是我们管理 irAE 的五个原则。由于基线肺功能脆弱,区分免疫诱导性肺炎与进展、假性进展、超进展或其他病因(COVID-19)在肺癌中可能特别具有挑战性,因此需要谨慎和团队合作。我们根据机构和国际指南治疗患者,并且只有在不良事件缓解和皮质类固醇逐渐减量后才重新使用 ICI。

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