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免疫检查点抑制剂引起的甲状腺功能障碍改善了癌症的预后。

Thyroid dysfunction caused by immune checkpoint inhibitors improves cancer outcomes.

机构信息

Department of Endocrinology and Nutrition, University of Navarra, Pamplona, Spain.

Department of Oncology, University of Navarra, Pamplona, Spain.

出版信息

Endocr Relat Cancer. 2024 Aug 8;31(10). doi: 10.1530/ERC-24-0064. Print 2024 Oct 1.

Abstract

A common immune-related adverse event (irAE) with immune checkpoint inhibitors (ICIs) is thyroid dysfunction (TD-irAEs). The clinical presentation can be varied, and its association with prognosis remains unclear. We investigated the characteristics of TD-irAEs and their association with clinical outcomes among cancer patients treated with ICIs in a real-life setting. Response to treatment was assessed using RECIST v1.1. We calculated the probability of recurrence and survival associated with TD-irAEs using multivariable-adjusted regression and Cox proportional hazards models. In this single-center retrospective analysis, we included 238 patients (72% male) with a median age of 69.5 years. Primary tumors were melanoma (23.1%), lung (60.5%), or urothelial cancer (16.4%), treated with atezolizumab (23.1%), pembrolizumab (44.5%), ipilimumab (0.4%), and/or nivolumab (25.6%). Seventy (29%) patients developed TD-irAEs in a median time of 69 days (41-181). The incidence of TD-irAEs with combination therapy was higher than with monotherapy (67% vs 6.3%, P = 0.011). TD-irAE patients showed a higher objective response rate (ORR) than those without TD-irAEs (60% vs 42.3%, P = 0.013) and longer overall survival (OS) 45 vs 16 months, P < 0.006. Patients who developed TD-irAEs had a relative reduction of 77% (OR 0.23, 95% CI 0.11-0.47) in the risk of progression and of 47% in the risk of mortality (HR 0.53, 95% CI 0.36-0.80), independent of age, sex, primary tumor, or ICI regimen. TD-irAEs occur in nearly 30% of our patients receiving ICIs. In our analysis, TD-irAEs appeared to be associated with higher ORR and longer OS and showed a reduction in the risk of progression and mortality.

摘要

免疫检查点抑制剂 (ICI) 常见的免疫相关不良事件 (irAE) 是甲状腺功能障碍 (TD-irAE)。临床表现多种多样,其与预后的关系尚不清楚。我们在真实环境中研究了接受 ICI 治疗的癌症患者中 TD-irAE 的特征及其与临床结局的关系。使用 RECIST v1.1 评估治疗反应。我们使用多变量调整回归和 Cox 比例风险模型计算与 TD-irAE 相关的复发和生存概率。在这项单中心回顾性分析中,我们纳入了 238 名(72%为男性)中位年龄为 69.5 岁的患者。主要肿瘤为黑色素瘤 (23.1%)、肺癌 (60.5%) 或尿路上皮癌 (16.4%),接受阿替利珠单抗 (23.1%)、帕博利珠单抗 (44.5%)、伊匹单抗 (0.4%) 和/或纳武单抗 (25.6%) 治疗。70 名(29%)患者在中位时间 69 天(41-181 天)出现 TD-irAE。联合治疗的 TD-irAE 发生率高于单药治疗(67% vs. 6.3%,P=0.011)。TD-irAE 患者的客观缓解率(ORR)高于无 TD-irAE 患者(60% vs. 42.3%,P=0.013),总生存期(OS)更长(45 个月 vs. 16 个月,P<0.006)。发生 TD-irAE 的患者进展风险降低 77%(OR 0.23,95%CI 0.11-0.47),死亡风险降低 47%(HR 0.53,95%CI 0.36-0.80),与年龄、性别、原发肿瘤或 ICI 方案无关。在接受 ICI 治疗的患者中,近 30%的患者出现 TD-irAE。在我们的分析中,TD-irAE 似乎与更高的 ORR 和更长的 OS 相关,并显示出降低进展和死亡风险的趋势。

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