Therapeutic guidance of tumor mutation burden on immune checkpoint inhibitors in advanced non-small cell lung cancer:a systematic review and comprehensive meta-analysis

作     者：Jie Zhao Yiting Dong Hua Bai Jianchun Duan Guoqiang Wang Jiachen Xu Jie Wang Zhijie Wang 

作者机构：State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina The Medical DepartmentBurning Rock BiotechGuangzhouChina 

出 版 物：《Journal of the National Cancer Center》 (癌症科学进展（英文）)

年 卷 期：2022年第2卷第1期

页      面：41-49页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Key Research and Devel-opment Project(2019YFC1315700) the National Natural Science Foundation of China(81871889,82072586) 

主　　题：Carcinoma Non-small cell lung Tumor mutation burden Immune checkpoint inhibitors Predictive biomarker Meta-analysis 

摘      要：Background:Tumor mutation burden(TMB)remains a promising but ambiguous predictive biomarker for the efficacy of immune checkpoint inhibitors(ICIs).We investigated the predictive value of TMB in patients with advanced non-small cell lung cancer(NSCLC)treated by ICI-containing therapies under strictly matched clinical ***:PubMed,Embase,Cochrane Central,***,and bioRxiv databases were searched till October 16,*** randomized controlled trials(RCTs)that compared patients with high TMB(TMB-H)and low TMB(TMB-L)and provided hazard ratio(HR)and corresponding 95%confidence interval(CI)in advanced NSCLC patients receiving ICIs were included,and mirror-based meta-analysis was performed(Part1).Bayesian network meta-analysis was conducted to investigate the efficacy of distinct first-line regimens in TMB-H and TMB-L groups(Part2).Public cohorts were used for validation and further exploration(Part3).Results:Twelve RCTs(n=5527)and 5 public cohorts(n=573)were *** Part1,TMB-H patients generally exhibited a more significant progression-free survival(PFS)benefit from ICI-containing therapies compared to TMB-L patients(HR=0.58,95%CI:0.49-0.67,P0.0001).In Part2,anti-PD-1 plus chemotherapy ranked best for PFS in both TMB-H and TMB-L ***-PD-L1 plus anti-CTLA-4 therapies indicated better PFS and overall survival(OS)benefit than single ICI and chemotherapy in the TMB-H group,but ranked worst in the TMB-L ***,TMB was validated to be an independent predictive biomarker from programmed cell death-ligand 1(PD-L1)expression in Part3,which could further distinguish beneficiaries of ICI-containing therapies with PD-L150%.Conclusion:TMB-H could be a predictive biomarker independent of PD-L1 expression to identify beneficiaries of ICI-containing therapy in advanced NSCLC patients.