免疫检查点抑制剂单药治疗时机和激素应用对晚期非小细胞肺癌脑转移疗效和安全性影响的Meta分析

Effect of timing of immune checkpoint inhibitor monotherapy and application of hormone on the efficacy and safety of brain metastasis in advanced non-small cell lung cancer:a Meta-analysis

目的评价程序性细胞死亡受体1(PD-1)、程序性细胞死亡受体配体1(PD-L1)免疫检查点抑制剂(ICI)单药治疗晚期非小细胞肺癌(NSCLC)脑转移的疗效和安全性,探讨免疫单药治疗时机和应用激素对ICI疗效的影响。方法通过检索中国知网、万方数据库、中文科技期刊全文数据库、PubMed、CBM、Embase、Cochrane Library、Web of Science数据库文献,确定纳入接受ICI治疗的晚期NSCLC脑转移患者,包括采用激素治疗或经颅脑手术或放疗的有症状的脑转移患者。对收集的数据进行Meta分析,评估全身系统客观反应率(sORR)和颅内肿瘤客观反应率(iORR)、ICI单药是否一线治疗的iORR以及是否应用激素的iORR,同时收集不良反应发生情况。结果最终纳入15项研究,患者共4033例,其中脑转移917例。单药免疫治疗iORR为26%(95%CI 19%~34%),sORR为28%(95%CI 18%~40%)。免疫单药一线治疗iORR为49%(95%CI 39%~58%)。有症状接受激素治疗和无症状未接受激素治疗患者的iORR分别是26%(95%CI 20%~33%)和19%(95%CI 16%~22%)。总体3~4级不良反应的发生率为14%(95%CI 11%~17%)。结论ICI单药一线治疗PD-L1阳性NSCLC脑转移的疗效优于其后线治疗,激素的应用未影响ICI疗效;ICI单药治疗晚期NSCLC脑转移安全性较好。

Objective To evaluate the efficacy and safety of programmed death 1(PD-1),programmed death ligand 1(PD-L1)immune checkpoint inhibitor(ICI)monotherapy for brain metastasis in advanced non-small cell lung cancer(NSCLC),and to explore the timing of immunomonotherapy and the application of hormone on the efficacy of ICI.Methods By searching literature in CNKI,Wanfang,VIP,PubMed,CBM,Embase,Cochrane Library and Web of Science databases,the advanced NSCLC patients with brain metastasis who received ICI treatment were identified,including patients with symptomatic brain metastasis who had received hormone therapy or brain surgery or radiotherapy.Meta-analysis was performed on the collected data to evaluate the systemic objective response rate(sORR)and intracerebral tumor objective response rate(iORR),the iORR of whether ICI monotherapy was first-line therapy,and the iORR of whether hormone was used were evaluated,and the incidence of adverse reactions was evaluated.Results Fifteen studies were finally included,with a total of 4033 patients,including 917 patients with brain metastasis.The iORR of immunomonotherapy was 26%(95%CI 19%-34%)and the sORR was 28%(95%CI 18%-40%).The iORR of first-line immunomonotherapy was 49%(95%CI 39%-58%).The iORR of symptomatic patients with hormone therapy and asymptomatic patients without hormone therapy was 26%(95%CI 20%-33%)and 19%(95%CI 16%-22%),respectively.The overall incidence of grade 3-4 adverse reactions was 14%(95%CI 11%-17%).Conclusions The efficacy of ICI monotherapy in the first-line treatment of PD-L1-positive NSCLC patients with brain metastasis is better than that in the subsequent line therapy,and the application of hormone does not affect the efficacy of ICI.ICI monotherapy in the treatment of advanced NSCLC patients with brain metastasis is safe.