Background The profile of immune-related adverse events (irAEs) due to programmed death-1 (PD-1) inhibitors-based combination therapy in advanced non-small cell lung cancer (NSCLC) and its relationship with survival have not been fully described. Objective Designed to capture the spectrum of irAEs and explore the association between irAEs and clinical outcomes in patients with NSCLC. Design This retrospective single-center study included patients with advanced NSCLC treated with PD-1 inhibitors (mainly in combination with chemotherapy) at Jiangsu Cancer Hospital. Methods The relationship between irAEs and survival was explored using landmark analysis and time-dependent Cox regression. The subgroup analyses focused on investigating the effects of organ-specific irAE, irAE grade, and steroid dose used to treat irAE. Results This study included 301 patients, 199 of whom received PD-1 inhibitors plus chemotherapy. The most common irAEs were skin toxicity (19.3%), endocrinopathy (21.3%), and pneumonitis (17.6%). In the entire cohort, the median progression-free survival (PFS) for patients developing and not developing irAE was 12.3 and 10.7 months (p < 0.001), and the median overall survival (OS) was 23.5 months and 20.1 months (p = 0.137), respectively. Subgroup analyses indicated that grade 3 or higher irAE, high steroid dose, and immune-related pneumonitis were detrimental to OS, whereas skin toxicity was beneficial to survival. These findings were further corroborated by both landmark analyses and Cox regression models conducted over four time points (1, 3, 6, and 12 months). Conclusion In the real world, NSCLC patients receiving PD-1 inhibitor-based combination therapy (particularly combined with chemotherapy) experience longer PFS with irAE, though not necessarily OS. Immune-related skin toxicity is associated with a better prognosis, whereas pneumonitis grade ⩾3 irAE and high steroid dose compromise survival. Clinicians should remain cognizant of the organ-specific manifestations of irAE and take proactive measures to mitigate the progression of irAE.

中文翻译：

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在接受基于程序性死亡 1 抑制剂的联合疗法治疗的非小细胞肺癌患者中，器官特异性免疫相关不良事件与生存之间的不同关联。

背景 晚期非小细胞肺癌 (NSCLC) 中基于程序性死亡 1 (PD-1) 抑制剂的联合治疗导致的免疫相关不良事件 (irAE) 的概况及其与生存的关系尚未得到充分描述。目的 旨在捕获 irAE 谱并探讨 irAE 与 NSCLC 患者临床结果之间的关联。设计这项回顾性单中心研究纳入了在江苏省肿瘤医院接受 PD-1 抑制剂（主要联合化疗）治疗的晚期 NSCLC 患者。方法 使用界标分析和时间依赖性 Cox 回归探讨 irAE 与生存之间的关系。亚组分析的重点是研究器官特异性 irAE、irAE 等级和用于治疗 irAE 的类固醇剂量的影响。结果本研究纳入了 301 名患者，其中 199 名患者接受了 PD-1 抑制剂加化疗。最常见的 irAE 是皮肤毒性（19.3%）、内分泌疾病（21.3%）和肺炎（17.6%）。在整个队列中，发生和未发生 irAE 的患者的中位无进展生存期 (PFS) 分别为 12.3 和 10.7 个月 (p < 0.001)，中位总生存期 (OS) 分别为 23.5 个月和 20.1 个月 (p = 0.137) ）， 分别。亚组分析表明，3 级或更高级别的 irAE、高类固醇剂量和免疫相关肺炎不利于 OS，而皮肤毒性则有利于生存。在四个时间点（1、3、6 和 12 个月）进行的里程碑分析和 Cox 回归模型进一步证实了这些发现。结论 在现实世界中，接受基于 PD-1 抑制剂的联合治疗（特别是联合化疗）的 NSCLC 患者在 irAE 的情况下经历了更长的 PFS，但不一定是 OS。免疫相关的皮肤毒性与更好的预后相关，而⩾3级irAE肺炎和高剂量类固醇会损害生存。临床医生应始终认识 irAE 的器官特异性表现，并采取积极措施减缓 irAE 的进展。