Hospices Civils de Lyon, Oncology Department, Pierre-Bénite, France; Université de Lyon, F-69000 Lyon, France; Université Lyon 1, F-69100 Villeurbanne, France; ImmuCare (Immunology Cancer Research) Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France.
Hospices Civils de Lyon, Oncology Department, Pierre-Bénite, France; Université de Lyon, F-69000 Lyon, France; Université Lyon 1, F-69100 Villeurbanne, France; ImmuCare (Immunology Cancer Research) Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France.
Eur J Cancer. 2020 Jun;132:61-70. doi: 10.1016/j.ejca.2020.03.017. Epub 2020 Apr 22.
The impact of immune-related adverse events (irAE) on survival outcomes after single-agent immune checkpoint inhibitors (ICIs) remains unclear. We aimed to evaluate the association between irAEs and ICI efficacy in various malignancies.
All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective multicentric series. The primary objective was to assess the impact of all type grade ≥II irAEs on progression-free survival (PFS) and overall survival (OS). IrAEs were first considered as a fixed covariate and included in Cox-regression models. In addition, as irAEs are time-related events and can occur at any point during follow-up, we analysed the occurrence of irAEs as a time-varying covariate.
In this cohort of 410 patients, the majority of patients (70%) were treated for non-small cell lung cancer. The ICI was an anti-PD(L)1 for 356 patients (82%) and an anti-CTLA4 for 79 patients (18%). In total 126 (29%) of the patients presented at least one grade ≥II irAEs. The first occurrence of a grade ≥II irAE had a positive impact on PFS and OS when considered as a fixed or as a time-varying covariate (hazard ratio [HR] for PFS = 0.63, 95% confidence interval [CI] 0.50-0.81; P = 0.00022; HR for OS = 0.57, 95% CI 0.43-0.74, P < 0.0001). This overall finding was confirmed in patients treated with an anti-PD(L)1 and among patients with lung cancer.
In this pooled multi-institutional cohort, the incidence of irAEs was associated with better long-term survival across different malignancies treated with ICI monotherapy.
免疫相关不良事件（irAE）对单药免疫检查点抑制剂（ICI）治疗后生存结局的影响尚不清楚。我们旨在评估不同恶性肿瘤中 irAE 与 ICI 疗效之间的关系。
本回顾性多中心研究纳入了所有接受单药 ICI 治疗的晚期癌症患者。主要目的是评估所有≥2 级的 irAE 对无进展生存期（PFS）和总生存期（OS）的影响。首先将 irAE 视为固定协变量并纳入 Cox 回归模型。此外，由于 irAE 是与时间相关的事件，并且可能在随访过程中的任何时间发生，因此我们将 irAE 的发生作为时变协变量进行分析。
在该 410 例患者队列中，大多数患者（70%）接受了非小细胞肺癌（NSCLC）的治疗。ICI 为抗 PD（L）1 药物者 356 例（82%），抗 CTLA4 药物者 79 例（18%）。共有 126 例（29%）患者出现至少 1 例≥2 级 irAE。当将首次发生≥2 级 irAE 视为固定或时变协变量时，irAE 的发生对 PFS 和 OS 均有积极影响（PFS 的 HR 为 0.63，95%CI 为 0.50-0.81；P=0.00022；OS 的 HR 为 0.57，95%CI 为 0.43-0.74，P<0.0001）。这一总体发现在接受抗 PD（L）1 治疗的患者和肺癌患者中得到了证实。
在本多机构队列中，irAE 的发生率与不同恶性肿瘤接受 ICI 单药治疗后的长期生存改善相关。
