免疫检查点抑制剂引起的垂体功能减退与恶性黑色素瘤和非小细胞肺癌的总生存改善相关：一项前瞻性研究。
Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study.
机构信息
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan
出版信息
J Immunother Cancer. 2020 Jul;8(2). doi: 10.1136/jitc-2020-000779.
BACKGROUND
Several immune-related adverse events (irAEs) are reported to be associated with therapeutic efficacy of immune checkpoint inhibitors, yet whether pituitary dysfunction, a life-threatening irAE, affects overall survival (OS) in patients with malignancies is unclear. This prospective study examined the association of pituitary dysfunction (pituitary-irAE) with OS of patients with non-small cell lung carcinoma (NSCLC) or malignant melanoma (MM).
METHODS
A total of 174 patients (NSCLC, 108; MM, 66) treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab at Nagoya University Hospital were evaluated for OS and the development of pituitary-irAE. Kaplan-Meier curves of OS as a function of the development of pituitary-irAE were produced with the log-rank test as a primary endpoint.
RESULTS
Pituitary-irAE was observed in 16 patients (4 (3.7%) with NSCLC, 12 (18.2%) with MM) having two different disease types: hypophysitis with deficiency of multiple anterior pituitary hormones accompanied by pituitary enlargement, and isolated adrenocorticotropic hormone (ACTH) deficiency without pituitary enlargement. Among these patients, 6 developed pituitary-irAE while being treated with ipilimumab (6/25 patients (24.0%) treated with ipilimumab) and 10 developed pituitary-irAE during treatment with nivolumab or pembrolizumab (10/167 (6.0%)). All 16 patients had ACTH deficiency and were treated with physiological doses of hydrocortisone. The development of pituitary-irAE was associated with better OS in patients with NSCLC (not reached vs 441 (95% CI not calculated) days, p<0.05) and MM (885 (95% CI 434 to 1336) vs 298 (95% CI 84 to 512) days, p<0.05).
CONCLUSIONS
In our study cohort, the incidence of pituitary-irAE was higher than previously reported and the development of pituitary-irAE predicted better prognosis for both NSCLC and MM when patients were treated with physiological doses of hydrocortisone.
CLINICAL TRIALS REGISTRATION
UMIN000019024.
背景
一些与免疫相关的不良反应（irAEs）与免疫检查点抑制剂的治疗效果相关，但危及生命的垂体功能障碍（pituitary-irAE）是否会影响恶性肿瘤患者的总生存期（OS）尚不清楚。本前瞻性研究检测了垂体功能障碍（pituitary-irAE）与非小细胞肺癌（NSCLC）或恶性黑色素瘤（MM）患者 OS 的相关性。
方法
共评估了在名古屋大学医院接受伊匹单抗、纳武单抗、帕博丽珠单抗或阿特珠单抗治疗的 174 例患者（NSCLC 108 例，MM 66 例）的 OS 和垂体-irAE 的发生情况。以 log-rank 检验为主要终点，制作了 OS 作为垂体-irAE 发生情况的函数的 Kaplan-Meier 曲线。
结果
16 例患者（NSCLC 4 例[3.7%]，MM 12 例[18.2%]）出现两种不同的疾病类型：伴有垂体增大的多种垂体前叶激素缺乏的垂体炎，以及不伴有垂体增大的孤立性促肾上腺皮质激素（ACTH）缺乏。这些患者中，6 例在接受伊匹单抗治疗时发生垂体-irAE（伊匹单抗治疗的 25 例患者中有 6 例[24.0%]），10 例在接受纳武单抗或帕博丽珠单抗治疗时发生垂体-irAE（167 例患者中有 10 例[6.0%]）。所有 16 例患者均有 ACTH 缺乏症，并用生理剂量的氢化可的松治疗。在 NSCLC 患者中（未达到 vs 441（95%CI 未计算）天，p<0.05）和 MM 患者中（885（95%CI 434 至 1336）vs 298（95%CI 84 至 512）天，p<0.05），垂体-irAE 的发生与更好的 OS 相关。
结论
在我们的研究队列中，垂体-irAE 的发生率高于先前报道的水平，当患者接受生理剂量的氢化可的松治疗时，垂体-irAE 的发生预测 NSCLC 和 MM 的预后更好。
临床试验注册
UMIN000019024。
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