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免疫相关不良事件及使用皮质类固醇治疗癌症相关症状与接受抗PD-(L)1阻断剂治疗的非小细胞肺癌患者的疗效相关。

Immune-Related Adverse Events and Corticosteroid Use for Cancer-Related Symptoms Are Associated With Efficacy in Patients With Non-small Cell Lung Cancer Receiving Anti-PD-(L)1 Blockade Agents.

作者信息

Riudavets Mariona, Mosquera Joaquin, Garcia-Campelo Rosario, Serra Jorgina, Anguera Georgia, Gallardo Pablo, Sullivan Ivana, Barba Andrés, Del Carpio Luís, Barnadas Agustí, Gich Ignasi, Majem Margarita

机构信息

Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Department of Medicine, Universitat Autónoma de Barcelona (UAB), Barcelona, Spain.

出版信息

Front Oncol. 2020 Sep 7;10:1677. doi: 10.3389/fonc.2020.01677. eCollection 2020.

Abstract

Immune-related adverse events (irAEs) have been associated with improved efficacy in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-(L)1 blockade agents, while the concurrent use of corticosteroids seems to worsen it. We evaluated outcomes in advanced NSCLC patients treated with anti-PD-(L)1 blockade agents in relation to the presence of irAEs and the reasons for using corticosteroids: whether for palliative cancer-related reasons or for the management of irAEs. Clinical outcomes in advanced NSCLC patients treated with anti-PD-(L)1 blockade agents were calculated with regard to the presence of irAEs and the use of corticosteroids. A landmark analysis was performed to avoid immortal time bias due to the time-dependent nature of irAEs. Out of a total of 267 patients, the 56.9% of patients who experienced irAEs had significantly improved outcomes. In the landmark analysis, median progression-free survival (PFS) was 12.4 months for patients with irAEs vs. 4.1 months for patients without irAEs ( < 0.001), while median overall survival (OS) was 28.2 vs. 12.5 months, respectively ( < 0.001). Likewise, objective response and disease control rates were significantly higher in patients experiencing irAEs: 48.6 vs. 22.8% and 77.1 vs. 39.6% ( < 0.001), respectively. Median OS was significantly shorter for patients receiving ≥10 mg of prednisone equivalent daily for cancer-related symptoms than for the rest of patients (<10 mg prednisone equivalent daily or for management of irAEs): 6 vs. 15.9 months ( < 0.001). IrAEs were associated with improved efficacy in advanced NSCLC patients when a landmark analysis was applied. Patients receiving corticosteroids had significantly poorer outcomes when they were used for cancer-related symptoms.

摘要

免疫相关不良事件(irAEs)与接受抗PD-(L)1阻断剂治疗的晚期非小细胞肺癌(NSCLC)患者疗效改善相关,而同时使用皮质类固醇似乎会使其恶化。我们评估了接受抗PD-(L)1阻断剂治疗的晚期NSCLC患者的结局,这些结局与irAEs的存在以及使用皮质类固醇的原因有关:是出于姑息性癌症相关原因还是用于管理irAEs。根据irAEs的存在情况和皮质类固醇的使用情况,计算接受抗PD-(L)1阻断剂治疗的晚期NSCLC患者的临床结局。由于irAEs具有时间依赖性,因此进行了一项标志性分析以避免不朽时间偏倚。在总共267例患者中,经历irAEs的患者中有56.9%的结局有显著改善。在标志性分析中,有irAEs的患者的无进展生存期(PFS)中位数为12.4个月,而无irAEs的患者为4.1个月(<0.001),而总生存期(OS)中位数分别为28.2个月和12.5个月(<0.001)。同样,经历irAEs的患者的客观缓解率和疾病控制率显著更高:分别为48.6%对22.8%和77.1%对39.6%(<0.001)。因癌症相关症状每天接受≥10 mg泼尼松等效剂量的患者的OS中位数明显短于其他患者(每天<10 mg泼尼松等效剂量或用于管理irAEs):6个月对15.9个月(<0.001)。应用标志性分析时,irAEs与晚期NSCLC患者的疗效改善相关。当皮质类固醇用于癌症相关症状时,接受皮质类固醇治疗的患者结局明显较差。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aea/7505083/f82b8e95bd10/fonc-10-01677-g0001.jpg

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