Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti 435, 20141, Milan, Italy.
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.
Curr Treat Options Oncol. 2021 Feb 8;22(3):19. doi: 10.1007/s11864-021-00817-4.
Immune checkpoint inhibitors (ICIs) represent a breakthrough in the management of many hard-to-treat cancers over the past decade with demonstrable improvement in survival outcomes. We reviewed the state of the art of ICIs in neuroendocrine neoplasms (NENs). While ICIs have become part of the standard of care for the management of small cell lung cancer (SCLC), their role is still unclear in the management of extra-pulmonary (EP) poorly differentiated neuroendocrine carcinomas (NECs) as well as in the management of well-differentiated neuroendocrine tumors (NETs). Conflicting results derived from the various studies in NETs and EP NECs therefore for specific settings, such as the lung NETs, or therapeutic regimen, e.g., combo vs single agent, for ICIs benefit. Therefore, at the moment, no ICIs approach is justified for NETs and EP NECs in clinical practice. Future investigations should be designed with the aim to overcome the several limitations of the current trials, e.g., lacking of a central pathology review or heterogeneity of the cohorts, in order to reduce the risk of biases. Future trials combining ICIs with other biological agents are welcome. This review aims to provide a comprehensive overview of the biological rationale and evolving clinical applications of the use of ICIs in the management of NENs (both well-differentiated and poorly differentiated groups).
免疫检查点抑制剂 (ICIs) 在过去十年中代表了许多难以治疗的癌症治疗的突破，在生存结果方面显示出明显的改善。我们回顾了 ICI 在神经内分泌肿瘤 (NENs) 中的应用现状。虽然 ICI 已成为小细胞肺癌 (SCLC) 管理标准护理的一部分，但它们在肺外 (EP) 低分化神经内分泌癌 (NEC) 以及高分化神经内分泌肿瘤 (NETs) 的管理中的作用仍不清楚。NETs 和 EP NEC 中的各种研究得出的相互矛盾的结果，因此在特定情况下，例如肺 NETs，或治疗方案，例如联合用药与单药治疗，ICI 可能会获益。因此，目前在临床实践中，没有任何 ICI 方法适用于 NETs 和 EP NECs。未来的研究应旨在克服当前试验的几个局限性，例如缺乏中心病理审查或队列的异质性，以降低偏倚风险。欢迎未来将 ICI 与其他生物制剂联合使用的试验。本综述旨在全面概述 ICI 在 NENs（包括高分化和低分化组）管理中的生物学原理和不断发展的临床应用。
