Charité - University Medicine Berlin, Department of Hepatology & Gastroenterology, Campus Virchow Klinikum and Charité Campus Mitte.
Charité - University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pathology.
Medicine (Baltimore). 2021 Jan 8;100(1):e23835. doi: 10.1097/MD.0000000000023835.
Immune check-point inhibitors (ICIs) have changed our view on how to treat cancer. Despite their approval in treatment of many different cancers, efficacy of immune check-point inhibitors (ICI) in neuroendocrine neoplasia is limited and poorly understood. Established treatment options of neuroendocrine tumors (NET) and neuroendocrine carcinomas (NECs) are based on surgery, tumor-targeted medical treatments, Peptide Receptor Radionuclide Therapy (PRRT), and locoregional therapies. However, in many patients these treatments lose efficacy over time, and novel therapies are urgently needed. We report on 8 patients diagnosed with neuroendocrine neoplasms (NEN) that were treated with ICI (pembrolizumab, avelumab, nivolumab plus ipilimumab) as salvage therapy. In this cohort, we observed tumor response with partial remission in 3 patients and stable disease in 1 patient. Four patients showed progressive disease. Of note, responses were observed both in PD-L1 positive and PD-L1 negative patients. Here, we discuss clinical courses of these patients in the context of available literature to highlight limitations and drawbacks currently preventing the use of ICI in routine management of patients with NEN.
免疫检查点抑制剂（ICIs）改变了我们对癌症治疗的看法。尽管它们已被批准用于治疗许多不同类型的癌症，但免疫检查点抑制剂（ICI）在神经内分泌肿瘤中的疗效有限且了解甚少。神经内分泌肿瘤（NET）和神经内分泌癌（NEC）的既定治疗选择基于手术、肿瘤靶向药物治疗、肽受体放射性核素治疗（PRRT）和局部区域治疗。然而，在许多患者中，这些治疗方法随着时间的推移会失去疗效，因此迫切需要新的治疗方法。我们报告了 8 例诊断为神经内分泌肿瘤（NEN）的患者，他们接受了 ICI（pembrolizumab、avelumab、nivolumab 加 ipilimumab）作为挽救治疗。在该队列中，我们观察到 3 例患者部分缓解，1 例患者疾病稳定。4 例患者出现疾病进展。值得注意的是，在 PD-L1 阳性和 PD-L1 阴性患者中均观察到了反应。在这里，我们根据现有文献讨论这些患者的临床过程，以突出目前限制和阻碍 ICI 在 NEN 患者常规管理中应用的局限性和缺点。
