程序性死亡受体-1抑制剂安全性的网状Meta分析

丁炟之, 祝伟伟, 杨洋, 李康琪, 程丽艳, 陆丛笑

中国药学杂志 ›› 2021, Vol. 56 ›› Issue (21) : 1770-1779.

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中国药学杂志
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中国药学杂志 ›› 2021, Vol. 56 ›› Issue (21) : 1770-1779. DOI: 10.11669/cpj.2021.21.011
论著

程序性死亡受体-1抑制剂安全性的网状Meta分析

  • 丁炟之1, 祝伟伟2, 杨洋1, 李康琪2, 程丽艳2, 陆丛笑2*
作者信息 +

A Network Meta-Analysis on the Safety of Programmed Cell Death 1 Inhibitors

  • DING Da-zhi1, ZHU Wei-wei2, YANG Yang1, LI Kang-qi2, CHENG Li-yan2, LU Cong-xiao2*
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文章历史 +

摘要

目的 利用网状Meta分析方法,对用程序性死亡受体-1(programmed cell death-1,PD-1)抑制剂的各种合并用药方法与化疗等传统抗肿瘤疗法的安全性进行比较。方法 在中英文数据库中检索PD-1抑制剂抗肿瘤治疗安全性的临床研究,截至2020年6月18日。用ADDIS软件进行网状Meta分析,探索PD-1抑制剂单药、PD-1抑制剂联合小分子靶向药物、化疗等多种抗肿瘤疗法之间的安全性差异。并对黑色素瘤、消化系统肿瘤、非小细胞肺癌和头颈癌等肿瘤患者的严重不良事件、不良事件结局进行亚组分析。结果 共纳入57项研究,包含11种干预措施,27 379名患者。对严重不良事件指标进行分析,排序图显示各干预措施的SAE发生概率从高到低的排序依次为:PD-1抑制剂联合小分子靶向药物、PD-1抑制剂联合CTLA-4抑制剂、PD-1抑制剂联合化疗药物、EGFR抑制剂联合化疗药物、化疗药物联合安慰剂、CTLA-4抑制剂单药、PD-1抑制剂联合安慰剂、小分子靶向药单药、PD-1抑制剂单药、安慰剂。对不良事件进行分析,排序图显示酪氨酸激酶(EGFR)抑制剂+化疗组的不良反应发生概率最高,最低的仍为安慰剂组,PD-1抑制剂次之。根据亚组分析结果,各干预措施在不同肿瘤患者中安全性不同。结论 PD-1抑制剂单药不良事件发生率较低,联合其他药物时,不良事件发生率增大。

Abstract

OBJECTIVE To use the network Meta-analysis method to compare the safety of various combination of interventions using programmed cell death-1 (PD-1) inhibitors and chemotherapy and other traditional anti-tumor therapies. METHODS The clinical studies on the safety of anti-tumor therapy including PD-1 inhibitors were searched in Chinese and English databases, as of 2020.06.18. Use ADDIS software to conduct network Meta-analysis to explore the safety differences between PD-1 inhibitors, PD-1 inhibitors combined with small molecule targeted drugs, chemotherapy and other anti-tumor therapies. Subgroup analysis of serious adverse events and adverse events in patients with melanoma, digestive system tumors, non-small cell lung cancer and head and neck cancer were also carried out. RESULTS A total of 57 studies were included, including 11 interventions, and 27 379 patients. Analyzing serious adverse events, the ranking chart shows that the placebo group has the lowest probability of SAE, followed by the PD-1 inhibitor single-drug group, and the combination therapy of PD-1 inhibitors and small molecule targeted drugs has the highest SAE probability. The ranking chart of adverse events showed that the tyrosine kinase (EGFR) inhibitor + chemotherapy group had the highest incidence of adverse events, and the placebo group got the lowest, followed by PD-1 inhibitors. According to the results of subgroup analysis, each intervention has different safety in different tumor patients. CONCLUSION When PD-1 inhibitors are combined with other drugs for anti-tumor therapy, the incidence of adverse events increases. PD-1 inhibitor mono-therapy has a lower incidence of adverse events on the basis of its efficacy.

关键词

程序性死亡受体-1 / 联合疗法 / 严重不良事件 / 不良事件 / 网状Meta分析

Key words

programmed cell death-1 inhibitor / combined therapy / serious adverse effect / adverse effect / network Meta-analysis

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丁炟之, 祝伟伟, 杨洋, 李康琪, 程丽艳, 陆丛笑. 程序性死亡受体-1抑制剂安全性的网状Meta分析[J]. 中国药学杂志, 2021, 56(21): 1770-1779 https://doi.org/10.11669/cpj.2021.21.011
DING Da-zhi, ZHU Wei-wei, YANG Yang, LI Kang-qi, CHENG Li-yan, LU Cong-xiao. A Network Meta-Analysis on the Safety of Programmed Cell Death 1 Inhibitors[J]. Chinese Pharmaceutical Journal, 2021, 56(21): 1770-1779 https://doi.org/10.11669/cpj.2021.21.011
中图分类号： R969.3   

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