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PD-1 抑制剂引起的甲状腺功能异常对非小细胞肺癌患者的生存有积极影响。

Thyroid function abnormality induced by PD-1 inhibitors have a positive impact on survival in patients with non-small cell lung cancer.

机构信息

Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China; West China School of Medicine, Sichuan University, Chengdu, China.

Sichuan Aerospace System Engineering Institute, Chengdu, China.

出版信息

Int Immunopharmacol. 2021 Feb;91:107296. doi: 10.1016/j.intimp.2020.107296. Epub 2020 Dec 23.

Abstract

BACKGROUND

Thyroid function abnormality (TFA) is a common immune-related adverse event (irAEs), but the association between it and the efficacy of programmed cell death protein 1 (PD-1) inhibitor in advanced non-small cell lung cancer (NSCLC) is finitely understood.

MATERIALS AND METHODS

We conducted a single center, retrospective study of advanced NSCLC patients who were treated with PD-1 inhibitors between 10 October 2016 and 1 April 2020. TFA was characterized as new onset subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism and overt hyperthyroidism. Frequency of development of TFA-irAEs, and its relationship with overall survival (OS) and progression free survival (PFS) were evaluated.

RESULTS

In our study, 191 patients were treated with PD-1 inhibitors. Among them, forty patients (20.9%) developed TFA, of whom 10 (5.2%) presented with subclinical hypothyroidism, 15 (7.9%) with overt hypothyroidism, 6 (3.1%) with subclinical hyperthyroidism and 9 (4.7%) with overt hyperthyroidism. Survival analysis showed that the OS (16.8 months vs. 11.1 months, p < 0.001) and PFS (10.4 months vs. 5.5 months, p < 0.001) were significantly longer in patients with TFA-irAEs than in those without TFA-irAEs. In subgroup analysis of hypothyroidism and hyperthyroidism groups, similar trends were also obtained for both OS and PFS. After adjusting for potential confounding variables, patients with TFA-irAEs had a lower mortality risk (HR 0.334, 95%CI 0.196-0.571) than those without TFA-irAEs.

CONCLUSIONS

TFA-irAEs is associated with enhanced PD-1 inhibitor efficacy in advanced NSCLC patients and it may be a biomarker for antitumor immune response.

摘要

背景

甲状腺功能异常(TFA)是一种常见的免疫相关不良事件(irAEs),但它与程序性死亡蛋白 1(PD-1)抑制剂在晚期非小细胞肺癌(NSCLC)中的疗效之间的关系尚未完全了解。

材料和方法

我们进行了一项单中心、回顾性研究,纳入了 2016 年 10 月 10 日至 2020 年 4 月 1 日期间接受 PD-1 抑制剂治疗的晚期 NSCLC 患者。TFA 的特征为新发亚临床甲状腺功能减退症、显性甲状腺功能减退症、亚临床甲状腺功能亢进症和显性甲状腺功能亢进症。评估了 TFA-irAEs 的发生频率及其与总生存期(OS)和无进展生存期(PFS)的关系。

结果

在我们的研究中,191 名患者接受了 PD-1 抑制剂治疗。其中,40 名(20.9%)患者发生了 TFA,其中 10 名(5.2%)患者出现亚临床甲状腺功能减退症,15 名(7.9%)患者出现显性甲状腺功能减退症,6 名(3.1%)患者出现亚临床甲状腺功能亢进症,9 名(4.7%)患者出现显性甲状腺功能亢进症。生存分析显示,发生 TFA-irAEs 的患者的 OS(16.8 个月比 11.1 个月,p<0.001)和 PFS(10.4 个月比 5.5 个月,p<0.001)均显著延长。在甲状腺功能减退症和甲状腺功能亢进症组的亚组分析中,OS 和 PFS 也呈现出相似的趋势。在校正潜在混杂因素后,发生 TFA-irAEs 的患者的死亡率风险较低(HR 0.334,95%CI 0.196-0.571)。

结论

TFA-irAEs 与晚期 NSCLC 患者接受 PD-1 抑制剂治疗的疗效增强相关,它可能是抗肿瘤免疫反应的生物标志物。

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