程序性细胞死亡蛋白-1抑制剂用于老年晚期非小细胞肺癌患者的文献分析

Literature Analysis of PD-1 Inhibitors in Elderly Patients with Advanced Non-small Cell Lung Cancer

目的评价程序性细胞死亡蛋白-1(PD-1)抑制剂治疗老年晚期非小细胞肺癌的疗效和安全性。方法检索中国临床肿瘤学会、美国国立综合癌症网络、美国癌症协会、欧洲肿瘤内科学会、PubMed、Ovid(Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials)、中国知网(CNKI)、万方数据库、维普数据库,纳入3个肿瘤学会发布的非小细胞肺癌和老年肿瘤相关指南及PD-1抑制剂治疗老年非小细胞肺癌临床研究,对纳入的文献进行描述性分析。结果共纳入文献9篇,包括系统评价3篇、临床试验2篇、真实世界研究亚组分析1篇、个案报道2篇、队列研究1篇。根据指南,PD-1抑制剂可以引入作为大多数无驱动基因的晚期非小细胞肺癌患者的新标准治疗方案。目前指南暂未根据患者年龄推荐PD-1抑制剂的给药方案。现有研究显示,PD-1抑制剂在老年人群的安全性与全人群相似。60~65岁老年患者可以从PD-1抑制剂治疗中获益,但年龄≥75岁患者人群中免疫检查点抑制剂的疗效存在争议。结论目前老年非小细胞肺癌患者使用PD-1抑制剂证据较多的是帕博利珠单抗和纳武利尤单抗,有限证据显示帕博利珠单抗治疗老年非小细胞肺癌患者有效且安全。PD-1抑制剂治疗老年非小细胞肺癌患者的证据匮乏,尤其缺乏真实世界研究。

Objective To evaluate the efficacy and safety of PD-1 inhibitors in the treatment of elderly patients with advanced non-small cell lung cancer.Methods Based on the method of literature retrieval,the academic websites(including Chinese,American and European societies of clinical oncology)and electronic databases(including PubMed,Ovid,Cochrane Database of systematic reviews,Cochrane Central Register of controlled trials,CNKI,Wanfang and VIP)were searched.The relevant guidelines for non-small cell lung cancer and elderly cancer published by the societies and the literatures about PD-1 inhibitors in the treatment of elderly non-small cell lung cancer were included for descriptive analysis.Results Nine articles were finally included in the analysis,including 3 systematic reviews,subgroup analysis of 2 clinical trials,and 1 real-world 2 case reports and 1 cohort study.The guidelines suggest that introducing PD-1 inhibitors will be a standard new approach for most patients with advanced non-small cell lung cancer without actionable oncogenic driver genes.The current guidelines do not recommend administration of PD-1 inhibitors according to the age.Existing studies shown that the safety outcomes of PD-1 inhibitors in elderly patients with non-small cell lung cancer were similar to the overall study population.Elderly patients between 60 and 65 may benefit from PD-1 inhibitor therapy,but the efficacy of immune checkpoint inhibitors is controversial in patients aged 75 years or older.Conclusion At present,pembrolizumab and nivolumab had more evidence when used in elderly patients with non-small cell lung cancer.The limited evidence shows that pembrolizumab is effective and safe for elderly patients with non-small cell lung cancer.There is a lack of evidence of PD-1 inhibitors in the treatment of elderly patients with non-small cell lung cancer,especially the lack of real-world research.