Efficacy Of PD-1/PD-L1 Immune Checkpoint Inhibitors For Advanced Nsclc According To PD-L1 Expression: A Meta-analysis

Objective:Programmed death 1(PD-1)/programmed death ligand 1(PD-L1)immune checkpoint inhibitors(ICIs)has shown remarkable efficacy in the treatment of cancer.The predictive value of PD-L1 expression for ICIs in the treatment of advanced non-small cell lung cancer(NSCLC)has raise wide attention,also with some controversies.We combined existing data by meta-analysis to analyze the efficacy of immune checkpoint inhibitors(ICIs)in patients with advanced non-small cell lung cancer(NSCLC)with different PD-L1 expression levels,and to provide a basis for the selection of the best benefited patients.Methods:Databases such as PubMed,Cochrane Library,Embase database,clinicaltrial.gov and the major international conferences such as ASCO,ESMO,WCLC were searched to select the qualified literatures according to the inclusion and exclusion criteria.We extracted the hazard ratio(HR)with corresponding 95% confidence intervals(CIs)for overall survival(OS)and progression free survival(PFS),and the objective response rate(ORR),according to three subgroups of PD-L1 ≥ 50%,PD-L1 1%~49% and PD-L1<1%.All analyses were used the program RevMan5.3,to analyze the efficacy of ICIs in patients with different PD-L1 expression levels compared with chemotherapy by outcome measures of OS,PFS and ORR.Results:Finally,11 literatures from 10 randomized controlled trials and a total of 6122 patients were included in the study,including 3349 in the ICIs group and 2828 in the chemotherapy group.The results were as follows:1.In patients with advanced NSCLC with PD-L1≥50%,ICIs therapy improved OS(HR=0.59,95%CI: 0.49-0.70,P < 0.00001),PFS(HR=0.68,95% CI: 0.56-0.82,P<0.0001),and ORR(RR=1.70,95%CI: 1.20-2.39,P=0.003)compared with chemotherapy.2.In patients with advanced NSCLC with PD-L1 1%~49%,ICIs were associated with longer OS than chemotherapy(HR=0.82,95%CI: 0.72-0.93,P=0.002),consistent with the results of second or later line therapy but not first line therapy.But the PFS(HR=1.02,95% CI: 0.86-1.21,P=0.8)and ORR(RR=0.81,95%CI: 0.65-1.00,P=0.05)were no statistical significances in these patients.3.In patients with advanced NSCLC with PD-L1 < 1%,ICIs improved OS(HR=0.78,95%CI:0.67-0.91,P=0.001)compared with chemotherapy,but the PFS(HR=1.00,95% CI:0.86-1.17,P=0.97)and ORR(RR=0.82,95% CI:0.54-1.24,P=0.34)were no statistical significances.Conclusion:1.The PD-L1 expression level may have predictive value for the treatment of ICIs in advanced NSCLC.Patients with PD-L1≥50% could be the best recipients of ICIs,who had benefit from ICIs both in first-line and second-line treatments.2.Patients with PD-L1 1%~49% and PD-L1< 1% also had OS benefits from ICIs in second or later line therapy,but not PFS or ORR benefit,and more evidence is needed for first-line treatment.