DataSheet_2_Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival.pdf

ObjectivesImmune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis.
Design and methodsSingle-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure.
ResultsNon-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 – 0.71) or both (HR 0.41, CI 0.25 – 0.64) but not in those who only developed non-endocrine irAEs.
ConclusionsWomen may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.

研究目的：免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）常伴随免疫相关不良事件（immune-related adverse events, irAEs），其中内分泌疾病（endocrinopathies）较为常见。本研究旨在明确接受ICIs治疗的癌症患者所发生的内分泌与非内分泌免疫相关不良事件的临床特征，明确其发生的危险因素，并探究内分泌与非内分泌免疫相关不良事件是否与癌症预后改善存在差异关联。
研究设计与方法：本研究为单中心回顾性队列研究，纳入接受至少1个周期ICIs治疗的晚期或转移性实体瘤患者（男性242例，女性151例，中位年龄65岁）。主要结局指标为研究期间任意免疫相关不良事件的发生率、总生存期以及治疗失败时间。
研究结果：本研究中，32%的患者发生非内分泌免疫相关不良事件，12%的患者发生内分泌免疫相关不良事件。原发性甲状腺功能异常是最常见的内分泌免疫相关不良事件（占比9.5%），且多数内分泌疾病患者需要接受永久性激素替代治疗。女性患者发生内分泌免疫相关不良事件的风险显著升高（P=0.017）。同时发生内分泌与非内分泌免疫相关不良事件的患者生存获益最为显著（总生存期：风险比（hazard ratio, HR）=0.16，95%置信区间（confidence interval, CI）=0.09~0.28）。仅发生内分泌免疫相关不良事件的患者（HR=0.49，95%CI=0.34~0.71）以及同时发生两类不良事件的患者（HR=0.41，95%CI=0.25~0.64）的治疗失败时间均显著延长，但仅发生非内分泌免疫相关不良事件的患者未观察到该获益。
研究结论：女性患者接受ICIs治疗后发生内分泌免疫相关不良事件的风险可能升高。本研究首次对比了内分泌与非内分泌免疫相关不良事件对患者生存期的影响。发生内分泌免疫相关不良事件或可为ICIs治疗带来生存获益，未来需开展前瞻性研究以阐明该现象的具体机制。