Guezour Nadia, Soussi Ghassen, Brosseau Solenn, Abbar Baptiste, Naltet Charles, Vauchier Charles, Poté Nicolas, Hachon Lorry, Namour Céline, Khalil Antoine, Trédaniel Jean, Zalcman Gérard, Gounant Valérie
Thoracic Oncology Department-Early Phases Unit CIC-1425 Inserm, Institut du Cancer AP-HP.Nord, Hôpital Bichat-Claude Bernard, 46 Rue Henri Huchard, 75018 Paris, France.
Université Paris Cité, 75018 Paris, France.
Cancers (Basel). 2022 Aug 11;14(16):3878. doi: 10.3390/cancers14163878.
Background: Immune checkpoint inhibitors (ICIs) have been a major advance in treating non-small-cell lung cancer (NSCLC). Programmed cell death protein-1/programmed death-ligand 1 blockade enhances immune function, mediating anti-tumor activity, yet causing immune-related adverse events (irAEs). We investigated the prognostic role of Grade 3−4 irAEs on overall survival (OS). Methods: This observational study recruited advanced NSCLC patients who received ICIs at Bichat-Claude Bernard University Hospital and in a community hospital, Saint-Joseph Foundation (Paris), between 1 January 2016 and 31 December 2019. Immunotherapy as a single-agent or double-drug combination was applied in the first and later lines. Univariable and multivariable analyses were instrumental in evaluating the prognostic impact of irAEs. Results: Overall, 201 consecutive ICI-treated patients were enrolled. High-grade irAEs (Grades 3−4) occurred in 36 patients (17.9%), including 11 (30.5%) cases of pneumonitis, 8 (22.2%) of colitis, 4 (11.1%) hepatic, 3 (8.3%) dermatological, 2 (5.5%) neurological events, and 2 cases (5.5%) of poly-arthralgia. The median OS was 10.4 ± 1.36 months (95% CI:7.7−13.1), being significantly higher in patients with high-grade irAEs than those without, 27.8 months vs. 8.1 months, respectively (HR = 2.5; p < 0.0001). Multivariable analysis revealed an independent association between high-grade irAEs and longer OS (HR = 0.29, 95% CI: 0.2−0.6, p < 0.0001). Conclusions: Our real-life study confirms that high-grade irAEs predict longer OS in advanced NSCLC.
免疫检查点抑制剂（ICIs）是治疗非小细胞肺癌（NSCLC）的一项重大进展。程序性细胞死亡蛋白1/程序性死亡配体1阻断可增强免疫功能，介导抗肿瘤活性，但会引发免疫相关不良事件（irAEs）。我们研究了3-4级irAEs对总生存期（OS）的预后作用。方法：这项观察性研究纳入了2016年1月1日至2019年12月31日期间在比夏特-克劳德·贝尔纳大学医院和圣约瑟夫基金会（巴黎）一家社区医院接受ICIs治疗的晚期NSCLC患者。免疫疗法作为单药或双药联合应用于一线及后续治疗。单变量和多变量分析有助于评估irAEs的预后影响。结果：总体而言，连续纳入了201例接受ICI治疗的患者。36例（17.9%）患者发生了高级别irAEs（3-4级），包括11例（30.5%）肺炎、8例（22.2%）结肠炎、4例（11.1%）肝脏疾病、3例（8.3%）皮肤病、2例（5.5%）神经系统事件和2例（5.5%）多关节痛。中位OS为10.4±1.36个月（95%CI：7.7-13.1），高级别irAEs患者的OS显著高于无高级别irAEs患者，分别为27.8个月和8.1个月（HR=2.5；p<0.0001）。多变量分析显示高级别irAEs与更长的OS之间存在独立关联（HR=0.29，95%CI：0.2-0.6，p<0.0001）。结论：我们的真实世界研究证实，高级别irAEs可预测晚期NSCLC患者更长的OS。
