Sugai Mayu, Amino Yoshiaki, Fujishima Shunsuke, Nibuya Kyujiro, Iso Hirokazu, Ito Masahiro, Tsugitomi Ryosuke, Ariyasu Ryo, Uchibori Ken, Yanagitani Noriko, Nishio Makoto
Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan.
Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan.
Lung Cancer. 2025 Jun;204:108555. doi: 10.1016/j.lungcan.2025.108555. Epub 2025 Apr 22.
Immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) may serve as prognostic markers in non-small cell lung cancer (NSCLC). While prior studies suggest differences in overall survival (OS) based on irAE, their prognostic impact across various ICI regimens remains underexplored.
This retrospective study analyzed data from patients with advanced or recurrent NSCLC treated with ICIs between January 2018 and December 2022. Patients were categorized into three groups: severe irAEs (Grade 3-5), mild irAEs (Grade 1-2), and no-irAEs. OS was assessed across three regimens: anti-programmed cell death protein 1 (anti-PD-1) monotherapy, anti-PD-1/anti-programmed death-ligand 1 (anti-PD-L1) with chemotherapy (CT), and anti-PD-1 with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) ± CT.
Among the 256 patients included, 55 received anti-PD-1 monotherapy, 116 received anti-PD-1/L1 with CT, and 85 received anti-PD-1 with anti-CTLA-4 ± CT. For anti-PD-1 monotherapy, median OS (95 % confidence interval) was 38.3 (17.0-42.5) months in the mild irAE group, 16.1 (5.2-28.6) months in the severe irAE group, and 9.6 (12.3-37.1) months in the no-irAE group. In the anti-PD-1/L1 with CT group, median OS were 33.6 (14.2-40.3), 16.0 (1.84-not reached [NR]), and 17.7 (3.8-23.4) months, respectively. For anti-PD-1 with anti-CTLA-4 ± CT, median OS were 28.0 (21.8-NR), 10.9 (7.0-19.6), and 16.3 (8.7-23.4) months, respectively.
The relationship between irAE severity and OS was consistent across all ICI regimens, with patients experiencing mild irAEs demonstrating better OS across all ICI regimens.
与免疫检查点抑制剂（ICI）相关的免疫相关不良事件（irAE）可能是非小细胞肺癌（NSCLC）的预后标志物。虽然先前的研究表明基于irAE的总生存期（OS）存在差异，但它们在各种ICI治疗方案中的预后影响仍未得到充分探索。
这项回顾性研究分析了2018年1月至2022年12月期间接受ICI治疗的晚期或复发性NSCLC患者的数据。患者被分为三组：严重irAE（3-5级）、轻度irAE（1-2级）和无irAE。在三种治疗方案中评估OS：抗程序性细胞死亡蛋白1（抗PD-1）单药治疗、抗PD-1/抗程序性死亡配体1（抗PD-L1）联合化疗（CT）以及抗PD-1联合抗细胞毒性T淋巴细胞相关蛋白4（抗CTLA-4）±CT。
在纳入的256例患者中，55例接受抗PD-1单药治疗，116例接受抗PD-1/L1联合CT治疗，85例接受抗PD-1联合抗CTLA-4±CT治疗。对于抗PD-1单药治疗，轻度irAE组的中位OS（95%置信区间）为38.3（17.0-42.5）个月，严重irAE组为16.1（5.2-28.6）个月，无irAE组为9.6（12.3-37.1）个月。在抗PD-1/L1联合CT组中，中位OS分别为33.6（14.2-40.3）、16.0（1.84-未达到[NR]）和17.7（3.8-23.4）个月。对于抗PD-1联合抗CTLA-4±CT，中位OS分别为28.0（21.8-NR）、10.9（7.0-19.6）和16.3（8.7-23.4）个月。
在所有ICI治疗方案中，irAE严重程度与OS之间的关系是一致的，所有ICI治疗方案中出现轻度irAE的患者OS更好。
