Therapeutic options for pituitary neuroendocrine tumours (PitNETs) refractory to temozolomide are scarce. Immune checkpoint inhibitors (ICIs), particularly inhibitors of the programmed cell death-1 (PD-1) pathway and its ligand (PD-L1), have been experimentally used in aggressive or metastatic PitNETs. We aimed to study the therapeutic usefulness of anti-PD-1 drugs in patients with aggressive or metastatic PitNETs. Published cases and case series involving patients with PitNETs treated with PD-1/PD-L1 inhibitors were reviewed. Demographic data, clinical–pathological features, previous therapies, drug dosage and posology, and the best radiological and biochemical responses, as well as survival data, were evaluated. We identified 29 cases of aggressive (n= 13) or metastatic (n= 16) PitNETs treated with PD-1/PD-L1 inhibitors. The hypersecretion of adrenocorticotropic hormone (ACTH) was documented in eighteen cases (62.1%), seven were prolactinomas (24.1%), and four were non-functioning PitNETs. All patients underwent various therapies prior to using ICIs. Overall, a positive radiological response (i.e., partial/complete radiological response and stable disease) was observed in eighteen of twenty-nine cases (62.1%), of which ten and four were ACTH- and prolactin-secreting PitNETs, respectively. Hormonal levels reduced or stabilised after using ICIs in 11 of the 17 functioning PitNET cases with available data (64.7%). The median survival of patients treated with ICIs was 13 months, with a maximum of 42 months in two ACTH-secreting tumours. Among 29 patients with PitNETs treated with PD-1/PD-L1 inhibitors, the positive radiological and biochemical response rates were 62.1% and 64.7%, respectively. Altogether, these data suggest a promising role of ICIs in patients with aggressive or metastatic PitNETs refractory to other treatment modalities.
对于替莫唑胺耐药的垂体神经内分泌肿瘤（PitNETs），治疗选择十分有限。免疫检查点抑制剂（ICIs），特别是程序性细胞死亡蛋白-1（PD-1）通路及其配体（PD-L1）的抑制剂，已在侵袭性或转移性PitNETs中进行了试验性应用。本研究旨在探讨抗PD-1药物在侵袭性或转移性PitNETs患者中的治疗价值。我们系统回顾了已发表的、涉及使用PD-1/PD-L1抑制剂治疗的PitNETs患者的病例及病例系列报告，评估了人口统计学数据、临床病理特征、既往治疗史、药物剂量与用法、最佳影像学与生化反应以及生存数据。共纳入29例接受PD-1/PD-L1抑制剂治疗的侵袭性（n=13）或转移性（n=16）PitNETs病例。其中18例（62.1%）存在促肾上腺皮质激素（ACTH）分泌过多，7例为泌乳素瘤（24.1%），4例为无功能PitNETs。所有患者在使用ICIs前均接受过多种治疗。总体而言，在29例患者中有18例（62.1%）观察到积极的影像学反应（即部分/完全影像学缓解和疾病稳定），其中分别有10例和4例为分泌ACTH和泌乳素的PitNETs。在有数据的17例功能性PitNETs病例中，11例（64.7%）在使用ICIs后激素水平下降或趋于稳定。接受ICIs治疗的患者中位生存期为13个月，其中两例分泌ACTH的肿瘤患者最长生存期达42个月。在29例接受PD-1/PD-L1抑制剂治疗的PitNETs患者中，积极的影像学和生化反应率分别为62.1%和64.7%。综上所述，这些数据表明，ICIs对于其他治疗方式无效的侵袭性或转移性PitNETs患者具有潜在的良好应用前景。
Therapeutical Usefulness of PD-1/PD-L1 Inhibitors in Aggressive or Metastatic Pituitary Tumours
肿瘤(癌症)患者之家