Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland.
Chair of Internal Medicine and Department of Internal Medicine in Nursing, Medical University of Lublin, Lublin, Poland.
PLoS One. 2021 Sep 29;16(9):e0257484. doi: 10.1371/journal.pone.0257484. eCollection 2021.
The aim of the study was to assess the occurrence and nature of immune-related endocrine adverse events (irAEs) among patients with non-small-cell lung cancer (NSCLC) treated with nivolumab.
The study group included 35 patients (15 women, 20 men, 65.8 ± 7.1 years) with NSCLC in stage IIIB (n = 16, 45.7%) and IV (n = 19,54.3%) who were treated with nivolumab.
Of the studied patients, 34.3% (n = 12) developed endocrine irAEs (irAE group): 22.9% (n = 8) hyperthyroidism and 8.6% (n = 3) hypothyroidism, and in one case, hypophysitis was observed. The median irAEs onset time was 2 months. In the group of patients with thyroid disorders, permanent hypothyroidism eventually developed in 58.3%. The severity of the analyzed irAEs ranged from mild to moderate (Grade 1-2); the case of hypophysitis was estimated as Grade 3. The comparison of progression-free survival time (PFS) between the two groups showed longer PFS in patients in the irAE group (p = 0.021). Patients with irAE were treated significantly longer with nivolumab and they received more doses of nivolumab, however in Cox analysis we did not find patients with irAE to experience progression later than patients without them.
Nivolumab therapy is associated with an increased risk of endocrine adverse effects, particularly thyroid dysfunction. Endocrine adverse effects can be successfully treated pharmacologically and usually do not require discontinuation of immunotherapy. The relationship between a better cancer prognosis in patients who developed endocrine irAE has not been found.
评估纳武利尤单抗治疗非小细胞肺癌（NSCLC）患者免疫相关内分泌不良事件（irAE）的发生和性质。
研究组纳入了 35 名 NSCLC IIIB 期（n=16，45.7%）和 IV 期（n=19，54.3%）患者，这些患者接受了纳武利尤单抗治疗。
在研究的患者中，34.3%（n=12）发生了内分泌 irAE（irAE 组）：22.9%（n=8）为甲状腺功能亢进，8.6%（n=3）为甲状腺功能减退，且有一例患者发生了垂体炎。irAE 的中位发病时间为 2 个月。在甲状腺疾病患者中，最终有 58.3%发展为永久性甲状腺功能减退。分析的 irAE 严重程度为轻度至中度（1-2 级）；垂体炎被评估为 3 级。对两组无进展生存期（PFS）进行比较，发现 irAE 组的 PFS 更长（p=0.021）。irAE 患者接受纳武利尤单抗治疗的时间明显更长，接受的纳武利尤单抗剂量也更多，但在 Cox 分析中，我们未发现 irAE 患者比未发生 irAE 患者更晚进展。
纳武利尤单抗治疗与内分泌不良事件风险增加相关，尤其是甲状腺功能障碍。内分泌不良事件可以通过药物治疗成功控制，通常不需要停止免疫治疗。尚未发现发生内分泌 irAE 的患者癌症预后更好。
