Development of thyroid dysfunction is associated with clinical response to PD-1 blockade treatment in patients with advanced non-small cell lung cancer
Development of thyroid dysfunction is associated with clinical response to PD-1 blockade treatment in patients with advanced non-small cell lung cancer
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DOI：
10.1080/2162402x.2017.1375642
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发表时间：
2018-01-01
期刊：
影响因子：
7.2
通讯作者：
Kim, Tae Hyuk
中科院分区：
文献类型：
--
作者：
Kim, Hye In;Kim, Mijin;Kim, Tae Hyuk
目的：阻断程序性细胞死亡蛋白1 （PD-1）与其配体（PD-L1）相互作用的药物是一种很有前景的药物。免疫相关不良事件（irAEs）可能与良好的临床结果相关，甲状腺功能障碍是最常见的irAE之一。我们评估了PD-1阻断期间甲状腺功能障碍与非小细胞肺癌（NSCLC）患者治疗效果的关系。实验设计：共有58例接受PD-1阻断治疗的IV期非小细胞肺癌患者入组。将患者分为甲状腺功能不全组和甲状腺功能正常组。比较两组患者的总生存期（OS）和无进展生存期（PFS）。采用Cox比例风险模型对患者、肿瘤和用药因素进行调整。根据甲状腺功能障碍的严重程度评估客观缓解率（RR）和持久控制率。结果：甲状腺功能障碍组的OS[中位数118.0 (73.0-267.0)vs. 71.0（28.0-160.0）天，log-rank P = 0.025]和PFS[中位数118.0 (73.0-267.0)vs. 61.0 (28.0-130.0), log-rank P = 0.014]更长。调整后，甲状腺功能障碍是预后良好的独立预测因素[调整后HR = 0.11 (95% CI) 0.01-0.92；0.38（0.17-0.85）。甲状腺功能障碍严重程度与持久控制率相关（趋势P = 0.008）。结论：PD-1阻断期间甲状腺功能障碍与治疗反应相关，可为晚期非小细胞肺癌患者的免疫监测提供补充信息。
Purpose: Drugs that blockade interaction between programmed cell-death protein 1 (PD-1) and its ligand (PD-L1) are promising. Immune-related adverse events (irAEs) might be associated with favorable clinical outcomes, and thyroid dysfunction is one of the most common irAE. We evaluated the association of thyroid dysfunction during PD-1 blockade with the treatment efficacy in patients with non-small cell lung cancer (NSCLC).Experimental Design: A total 58 patients with stage IV NSCLC treated with PD-1 blockade were enrolled. Patients were categorized into thyroid dysfunction and euthyroid groups. Overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Patients, tumor, and medication factors were adjusted using Cox proportional hazard modeling. Objective response rate (RR) and durable control rate were assessed according to the severity of thyroid dysfunction.Results: OS [median 118.0 (73.0-267.0) vs. 71.0 (28.0-160.0) days, log-rank P = 0.025] and PFS [118.0 (73.0-267.0) vs. 61.0 (28.0-130.0), log-rank P = 0.014] were longer in the thyroid dysfunction group. After adjustment, thyroid dysfunction was an independent predictive factor for favorable outcome [adjusted HR = 0.11 (95% CI) 0.01-0.92 for overall death; 0.38 (0.17-0.85) for disease progression]. The severity of thyroid dysfunction was associated with durable control rate (P for trend = 0.008).Conclusions: Thyroid dysfunction during PD-1 blockade is associated with treatment response and could provide supplementary information for immune monitoring in patients with advanced NSCLC.