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PD-1/PD-L1抑制剂在乳腺癌中的相关不良事件及其管理

PD-1/PD-L1 Inhibitor - Related Adverse Events and Their Management in Breast Cancer.

作者信息

Lei Chuqi, Kong Xiangyi, Li Yuan, Yang Huaiyu, Zhang Ke, Wang Zhongzhao, Chang Hu, Xuan Lixue

机构信息

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Administration Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

出版信息

J Cancer. 2024 Mar 17;15(9):2770-2787. doi: 10.7150/jca.85433. eCollection 2024.

Abstract

As the positive results of multiple clinical trials were released, the Programmed cell death 1 (PD-1) and Programmed cell death ligand 1 (PD-L1) inhibitors emerge as the focus of integrative breast cancer treatment. PD-1/PD-L1 inhibitors are often used as a sequential agent to be combined with other agents such as chemotherapeutic agents, targeted agents, and radiation therapy. As multiple therapies are administered simultaneously or in sequence, they are prone to a variety of adverse effects on patients while achieving efficacy. It is a challenge for clinicians to maintaining the balance between immune-related adverse effects(irAEs) and treatment efficacy. Previous literatures have paid lots of attention on the adverse effects caused by immunosuppressive agents themselves, while there is a dearth of the research on the management of adverse immune effects during the combination of immunotherapy with other treatments. In this review, we discuss the overall incidence of irAEs caused by PD-1/PD-L1 inhibitors in combination with various types of treatments in breast cancer, including chemotherapy, CTLA-4 inhibitors, targeted therapy, and radiotherapy, and systematically summarizes the clinical management to each organ-related adverse immune reaction. It is important to emphasize that in the event of irAEs such as neurological, hematologic, and cardiac toxicity, there is no alternative treatment but to terminate immunotherapy. Thus, seeking more effective strategy of irAEs' management is imminent and clinicians are urged to raise the awareness of the management of adverse immune reactions.

摘要

随着多项临床试验阳性结果的公布,程序性细胞死亡蛋白1(PD-1)和程序性细胞死亡配体1(PD-L1)抑制剂成为乳腺癌综合治疗的焦点。PD-1/PD-L1抑制剂常作为序贯用药,与化疗药物、靶向药物和放射治疗等其他药物联合使用。由于多种治疗同时或序贯进行,在取得疗效的同时,它们容易对患者产生各种不良反应。临床医生要在免疫相关不良反应(irAEs)和治疗疗效之间保持平衡是一项挑战。以往文献较多关注免疫抑制剂本身所引起的不良反应,而对于免疫治疗与其他治疗联合过程中不良免疫反应的管理研究较少。在本综述中,我们讨论了PD-1/PD-L1抑制剂联合乳腺癌各种类型治疗(包括化疗、CTLA-4抑制剂、靶向治疗和放疗)所引起的irAEs的总体发生率,并系统总结了针对各器官相关不良免疫反应的临床管理。需要强调的是,一旦出现如神经、血液和心脏毒性等irAEs情况,除终止免疫治疗外别无他法。因此,寻求更有效的irAEs管理策略迫在眉睫,临床医生应提高对不良免疫反应管理的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fb5/10988294/17ddb0156ffd/jcav15p2770g001.jpg

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