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
Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Department of Medicine, Universitat Autónoma de Barcelona (UAB), Barcelona, Spain.
Front Oncol. 2020 Sep 7;10:1677. doi: 10.3389/fonc.2020.01677. eCollection 2020.
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.
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。
