PD-L1水平在PD-(L)1抑制剂治疗晚期实体肿瘤中疗效预测价值的Meta分析

Meta-analysis of Predictive Value of PD-L1 Levels in the Treatment of PD-(L)1 Inhibitors in Advanced Solid Tumors

目的:评估细胞程序性死亡-配体1(PD-L1)程序性细胞死亡受体1(PD-1)水平在PD-1/PD-L1抑制剂[PD-(L)1]治疗晚期实体肿瘤中的疗效预测价值。方法:系统检索了PubMed、CNKI、万方等数据库,收集PD-(L)1抑制剂治疗恶性肿瘤患者的相关研究,检索时限为各数据库建库至2022年12月28日。由两名研究者独立评价纳入研究的质量并提取资料,采用Stata 16.0和Rev Man 5.4进行Meta分析。结果:Meta分析结果显示,PD-L1阳性和阴性的晚期实体瘤患者在PD-(L)1抑制剂的治疗总生存期(OS)中差异无统计学意义(P>0.05),同样在常规药物治疗中二者有效性差异无统计学意义(P>0.05);与常规药物相比,PD-(L)1抑制剂显著延长PD-L1表达阳性患者和PD-L1阴性患者的OS;基于药物靶点、疾病、免疫组化评分类型和中位随访时间等方面亚组分析进一步佐证了以上结果。结论:PD-L1的表达状态(以1%为临界值)不足以作为预测使用PD-(L)1抑制剂治疗患者的OS;PD-L1阳性及阴性晚期肿瘤患者均可从抑制剂及常规药物治疗中获益;无论PD-L1的表达状态如何,与常规药物相比,PD-(L)1抑制剂都显著延长了晚期实体肿瘤患者的OS。

Objective:To evaluate the predictive value of PD-L1 expression of PD-1 in PD-1/PD-L1 inhibitor treatment of advanced solid tumors.Methods:PubMed,CNKI,WANFANG and other databases were systematically searched to collect studies of PD-(L)1 inhibitors in the treatment of patients with malignant tumors from the establishment of each database to December 28,2022.Two researchers independently evaluated the quality of included studies and extracted data.Stata16.0 and Rev Man5.4 were used for meta-analysis.Results:A total of 20 studies with a total of 12333 patients were included in this study.The results of meta-analysis showed that there was no statistically significant difference in overall survival(OS)of patients with PD-L1 positive and negative advanced solid tumors treated with PD-(L)1 inhibitors(P>0.05),and there was also no significant difference in the effectiveness of conventional drug therapy(P>0.05).Compared with conventional drugs,PD-(L)1 inhibitors significantly prolonged the OS in PD-L1 positive patients and PD-L1 negative patients.Subgroup analysis based on drug target,disease,immunohistochemical score type,and median follow-up time further supported these results was done.Conclusion:The expression status of PD-L1(1%as the cut-off value)is not sufficient to predict OS in patients treated with PD-(L)1 inhibitors.PD-L1 positive and negative advanced tumor patients can benefit from inhibitors and conventional drug treatment.Regardless of PD-L1 expression status,PD-(L)1 inhibitors significantly prolong OS in patients with advanced solid tumors compared with conventional drugs.