接受检查点抑制剂免疫治疗后出现内分泌并发症的肿瘤患者具有更长的无进展生存期和总生存期。
Oncological Patients With Endocrine Complications After Immunotherapy With Checkpoint Inhibitors Present Longer Progression-Free and Overall Survival.
作者信息
Paschou Stavroula A, Liontos Michael, Eleftherakis-Papaiakovou Evangelos, Stefanaki Katerina, Markellos Christos, Koutsoukos Konstantinos, Zagouri Flora, Psaltopoulou Theodora, Dimopoulos Meletios-Athanasios
机构信息
Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
出版信息
Front Oncol. 2022 Mar 24;12:847917. doi: 10.3389/fonc.2022.847917. eCollection 2022.
AIM
The aim of this study was to investigate the association of endocrine complications after ICI immunotherapy with progression-free survival (PFS) and overall survival (OS) in a large single-center oncological cohort.
PATIENTS AND METHODS
In total, 351 patients were included in the analysis, 248 men (70.7%) and 103 women (29.3%). The median age was 66 years. Patients had a variety of cancer types, namely, bladder cancer (131, 37.3%), renal cancer (89, 25.4%), lung cancer (74, 21.1%), ovarian cancer (22, 6.3%), and other types of cancer (35, 10%). The majority (314, 89.4%) were classified as stage IV, while 10.6% (37) were classified as stage III. Most of the patients received immunotherapy with anti-PD1 agents (262, 74.6%) and the rest with anti-PD-L1 agents (89, 25.4%). Kaplan-Meier estimates were used to describe and visualize the effect of categorical variables on OS and PFS. Survival analysis was performed by Kaplan-Meier curves, and survival differences between groups were estimated using the log-rank test. The estimation of the prognostic value of several variables with patients' survival was made by Cox regression models.
RESULTS
In total, 68 (19.4%) of patients presented an endocrine complication after immunotherapy with ICIs. Specifically, 66 (18.8%) had thyroid dysfunction, 1 patient presented hypophysitis (0.3%), and 1 patient had a combination of thyroid dysfunction and hypophysitis (0.3%). Patients with an endocrine complication had mPFS of 15 months (95% CI 11.0-18.9 months), while in those without endocrine complication mPFS was 7 months (95% CI 6.1-7.9 months, < 0.001). Similarly, median OS (mOS) was statistically significant lower in the patients' group without endocrine complication. In fact, mOS was 51 months (95% CI 39.3-62.7 months) for these patients. The presence of endocrine complications after immunotherapy with ICIs retained its significance in terms of longer PFS (HR 0.57, 95% CI 0.39-0.81) and OS (HR 0.53, 95% CI 0.32-0.90) after multivariate analysis.
CONCLUSIONS
ICI endocrinopathies may be a positive predictor of immunotherapy response.
目的
本研究旨在调查在一个大型单中心肿瘤队列中，ICI免疫治疗后内分泌并发症与无进展生存期（PFS）和总生存期（OS）之间的关联。
患者与方法
总共351例患者纳入分析，其中男性248例（70.7%），女性103例（29.3%）。中位年龄为66岁。患者患有多种癌症类型，即膀胱癌（131例，37.3%）、肾癌（89例，25.4%）、肺癌（74例，21.1%）、卵巢癌（22例，6.3%）以及其他类型癌症（35例，10%）。大多数（314例，89.4%）被分类为IV期，而10.6%（37例）被分类为III期。大多数患者接受抗PD1药物免疫治疗（262例，74.6%），其余接受抗PD-L1药物治疗（89例，25.4%）。采用Kaplan-Meier估计来描述和可视化分类变量对OS和PFS的影响。通过Kaplan-Meier曲线进行生存分析，并使用对数秩检验估计组间生存差异。通过Cox回归模型评估几个变量对患者生存的预后价值。
结果
总共68例（19.4%）患者在ICI免疫治疗后出现内分泌并发症。具体而言，66例（18.8%）有甲状腺功能障碍，1例出现垂体炎（0.3%），1例同时有甲状腺功能障碍和垂体炎（0.3%）。有内分泌并发症的患者mPFS为15个月（95%CI 11.0 - 18.9个月），而无内分泌并发症的患者mPFS为数月（95%CI 6.1 - 7.9个月，<0.001）。同样，无内分泌并发症患者组的中位OS（mOS）在统计学上显著更低。实际上，这些患者的mOS为51个月（95%CI 39.3 - 62.7个月）。在多变量分析后，ICI免疫治疗后内分泌并发症的存在在更长的PFS（HR 0.57，95%CI 0.39 - 0.81）和OS（HR 0.53，95%CI 0.32 - 0.90）方面仍具有显著性。
结论
ICI内分泌病可能是免疫治疗反应的一个阳性预测指标。
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