Campredon Pauline, Mouly Céline, Lusque Amélie, Bigay-Game Laurence, Bousquet Emilie, Mazières Julien, Caron Philippe
CHU Larrey, Department of endocrinology and metabolic diseases, 31059 Toulouse, France.
Institut Claudius-Regaud, IUCT-O, Department of statistics, 31100 Toulouse, France.
Presse Med. 2019 Apr;48(4):e199-e207. doi: 10.1016/j.lpm.2018.10.019. Epub 2019 Apr 17.
Immunotherapy is a standard not only in second line but also in first line treatment in patients with non-small cell lung cancer (NSCLC) and other tumors. Thyroid dysfunctions are the most common endocrine toxicities.
To determine the incidence of thyroid dysfunctions during treatment with a PD-1 monoclonal antibody (nivolumab) in patients with NSCLC.
Retrospective study of patients treated with nivolumab for NSCLC between May 2015 and December 2016; euthyroidism within the 3 months preceding immunotherapy; monitoring of thyroid function tests until stopping nivolumab, death or February 2017. Patients treated with levothyroxine, amiodarone or another immunotherapy were excluded.
Among 183 patients treated, 105 fullfilled the inclusion criteria (72 males, median age: 61 years [range: 41-80]). Fifteen patients (14.3%) experienced a thyroid dysfunction; among them, compared to the "control" group (n=90), we found more females (53.3% vs. 27.8%; P=0.07), and younger patients (median age: 56 years vs. 62 years; P=0.02). Thirteen patients had thyrotoxicosis (median onset: 8 weeks), and then hypothyroidism was observed in 5 patients. Isolated hypothyroidism was rare (n=2) and late (median: 30 weeks). Three patients had anti-TPO antibodies. Three patients discontinued immunotherapy transiently due to thyroid dysfunctions. After a median follow-up of 9 months [95% CI, 7.5-10.3], one patient (6.7%) in the "thyroid dysfunctions" group and 30 patients (33.3%) in the "control" group died, with a trend toward a higher overall survival in the "thyroid dysfunctions" group (HR: 0.16 [95% CI, 0.02-1.15]; P=0.07).
Thyroid dysfunctions (isolated thyrotoxicosis, biphasic thyroiditis and hypothyroidism) were common, and required patients with NSCLC to be screened during nivolumab therapy.
免疫疗法不仅是晚期非小细胞肺癌（NSCLC）患者二线治疗的标准方案，也是一线治疗的标准方案，在其他肿瘤治疗中亦是如此。甲状腺功能障碍是最常见的内分泌毒性反应。
确定NSCLC患者接受程序性死亡受体1（PD-1）单克隆抗体（纳武单抗）治疗期间甲状腺功能障碍的发生率。
回顾性研究2015年5月至2016年12月期间接受纳武单抗治疗的NSCLC患者；免疫治疗前3个月甲状腺功能正常；监测甲状腺功能直至停用纳武单抗、患者死亡或2017年2月。排除接受左甲状腺素、胺碘酮或其他免疫治疗的患者。
在183例接受治疗的患者中，105例符合纳入标准（男性72例，中位年龄61岁[范围：41-80岁]）。15例患者（14.3%）出现甲状腺功能障碍；其中，与“对照组”（n=90）相比，女性更多（53.3%对27.8%；P=0.07），且患者更年轻（中位年龄：56岁对62岁；P=0.02）。13例患者发生甲状腺毒症（中位发病时间：8周），随后5例患者出现甲状腺功能减退。孤立性甲状腺功能减退很少见（n=2）且出现较晚（中位时间：30周）。3例患者有抗甲状腺过氧化物酶抗体。3例患者因甲状腺功能障碍短暂停用免疫治疗。中位随访9个月[95%CI，7.5-10.3]后，“甲状腺功能障碍”组1例患者（6.7%）和“对照组”30例患者（33.3%）死亡，“甲状腺功能障碍”组总体生存率有升高趋势（HR：0.16[95%CI，0.02-1.15]；P=0.07）。
甲状腺功能障碍（孤立性甲状腺毒症、双向性甲状腺炎和甲状腺功能减退）很常见，NSCLC患者在接受纳武单抗治疗期间需要进行筛查。
