Department of Endocrinology and Nutrition, University of Navarra, Pamplona, Spain.
Department of Oncology, University of Navarra, Pamplona, Spain.
Endocr Relat Cancer. 2024 Aug 8;31(10). doi: 10.1530/ERC-24-0064. Print 2024 Oct 1.
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.
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。
