Objective: To assess the incidence and characteristics of thyroid dysfunction during anti-Programmed cell death 1 receptor (PD-1) antibody SHR-1210 therapy in patients with advanced solid tumor. Methods: The medical records of 98 patients who initiated SHR-1210 treatment between April 27, 2016 and June 8, 2017 in the phase 1 trial to evaluate the safety, efficacy, and pharmacokinetics of SHR-1210 in patients with advanced solid tumors were retrospectively reviewed. Serological tests of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at baseline and prior to each SHR-1210 administration. Results: A total of 86 patients had normal thyroid function before the first dose of SHR-1210 treatment. Nine out of 86 (10.5%) patients developed new onset hypothyroidism from euthyroid state. 12 patients presented thyroid dysfunction at baseline, 10 of whom were subclinical hypothyroid and 2 were hypothyroidism. Four out of 10 patients developed hypothyroidism from subclinical hypothyroid. Most patients with hypothyroidism were asymptomatic. Thyroid dysfunction occurred early (median, 55days) after the initiation of SHR-1210. The severity of hypothyroidism were all grade 1-2. No grade 3-4 hypothyroidism occurred. No patients discontinue the treatment of SHR-1210 due to clinical impact of the thyroid dysfunctions. Conclusions: Thyroid-related adverse events were common during anti-PD-1 antibody SHR-1210 treatment . The incidence of hypothyroidism is lower in patients with euthyroid state than in patients with thyroid dysfunction at baseline during SHR-1210 treatment . Thyroid function can be improved after thyroid hormone replacement. During SHR-1210 treatment, it is necessary to pay attention to monitor the thyroid function, especially in the patients with thyroid dysfunction at baseline. Trial registration: Chinese Clinical Trial Registry, 2016L01455.
目的： 探讨程序性死亡蛋白1(PD－1)抗体SHR－1210治疗晚期实体瘤中甲状腺功能相关不良反应的发生情况。 方法： 回顾性分析2016年4月27日至2017年6月8日，入组PD－1抗体SHR－1210对晚期实体瘤的安全性及耐受性评价的Ⅰ期临床研究中98例患者的临床资料，分析患者血清中游离甲状腺素和血清促甲状腺素水平。 结果： 基线甲状腺功能正常的86例患者中，在SHR－1210治疗过程中新发甲状腺功能减退症9例(10.5%)；在基线甲状腺功能异常的12例患者中，有10例为基线亚临床甲状腺功能减退症，其中4例在用药过程中发展为甲状腺功能减退症。大部分发生甲状腺功能减退症的患者均无典型临床表现，仅在化验时发现甲状腺功能异常。首次试验用药至发现甲状腺功能异常的中位时间为55 d。在SHR－1210用药过程中，无Ⅲ～Ⅳ级甲状腺相关不良反应，无因甲状腺不良反应需停药的患者。 结论： 在PD－1抗体SHR－1210的用药过程中，与基线甲状腺功能异常患者比较，基线甲状腺功能正常的患者发生甲状腺功能减退症的概率更低。甲状腺功能减退症均为Ⅰ～Ⅱ级，给予甲状腺激素替代治疗后，甲状腺功能好转。在PD－1抗体SHR－1210用药过程中需监测甲状腺功能，尤其关注基线甲状腺功能异常的患者。 临床试验注册： 国家食品药品监督管理局临床研究，2016L01455.
Keywords: Adverse events; Immunotherapy; Neoplasms; Thyroid; anti-PD-1 antibody.