Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong Special Administrative Region.
State Key Laboratory of Translational Oncology, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
Oral Oncol. 2021 Feb;113:105127. doi: 10.1016/j.oraloncology.2020.105127. Epub 2021 Jan 14.
Upregulation of the programmed cell death receptor-1 and ligand (PD-1/PD-L1) pathway is one of many possible mechanisms of immune-evasion relevant to Epstein-Barr virus (EBV)- associated nasopharyngeal cancer (NPC). The therapeutic targeting of the PD-1/ PD-L1 axis is an area of active research in NPC and at least 8 monoclonal or bi-specific antibodies targeting this axis are currently under clinical evaluation in some of the following clinical settings: (1) palliative treatment of recurrent and/or metastatic (R/M) disease; (2) radical treatment of locoregionally advanced disease in adjunct to conventional chemoradiotherapy; (3) local/ regional recurrence. PD-1 antibodies as monotherapy has been reported to yield an overall objective response in around 20-30% of patients with R/M NPC in single-armed phase II trials, and the predictive role of PD-L1 expression in NPC remains to be defined. As with other solid tumors, combinatorial strategies with cytotoxic chemotherapy, radiotherapy or other immunotherapeutic agents (such as other immune-checkpoint inhibitors, EBV-targeting cellular therapy and other immune-modulating agents) and vascular endothelial growth factor/receptor antibodies are actively being evaluated in clinical trials with single-armed or randomized designs. This article will review the scientific rationale of targeting the PD1/PD-L1 axis in NPC, and summarizes the latest trials involving these agents and predictive biomarkers of response to PD-1/PD-L1 antibodies in NPC.
程序性细胞死亡受体-1 和配体（PD-1/PD-L1）通路的上调是与 Epstein-Barr 病毒（EBV）相关的鼻咽癌（NPC）相关的许多免疫逃逸机制之一。PD-1/PD-L1 轴的治疗靶向是 NPC 中一个活跃的研究领域，目前至少有 8 种针对该轴的单克隆或双特异性抗体正在以下一些临床环境中进行临床评估：（1）姑息治疗复发性和/或转移性（R/M）疾病；（2）局部区域晚期疾病的根治性治疗，辅助常规放化疗；（3）局部/区域复发。在单臂二期临床试验中，PD-1 抗体单药治疗报告在大约 20-30%的 R/M NPC 患者中产生总体客观缓解，PD-L1 表达在 NPC 中的预测作用仍有待确定。与其他实体瘤一样，联合细胞毒性化疗、放疗或其他免疫治疗药物（如其他免疫检查点抑制剂、EBV 靶向细胞治疗和其他免疫调节药物）和血管内皮生长因子/受体抗体的组合策略正在单臂或随机设计的临床试验中进行积极评估。本文将综述靶向 NPC 中 PD1/PD-L1 轴的科学原理，并总结涉及这些药物和 NPC 中 PD-1/PD-L1 抗体反应预测生物标志物的最新试验。
