Efficacy And Immune-Related Adverse Events Induced By PD-1/PD-L1 Inhibitors As First-Line Treatment For Advanced Non-Small Cell Lung Cancer:a Meta-Analysis Of Randomized Controlled Trials

Purpose: This meta-analysis was conducted to evaluate the efficacy and immunerelated adverse reactions(ir AEs)of anti-programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)monotherapy or immunotherapy combined with chemotherapy among non-small cell lung cancer(NSCLC)patients.Methods:Electronic databases(Pub Med,EMBASE,and the Cochrane library)and major conference proceedings were systematically searched for all clinical trials in NSCLC using PD-1/PD-L1 inhibitors.Randomized controlled trials(RCTs)were included to compare PD-1/PD-L1 inhibitor monotherapy or plus chemotherapy with chemotherapy in advanced NSCLC patients reporting progression-free survival(PFS),overall survival(OS),objective response rate(ORR),treatment related adverse events(TRAEs),and immune-related adverse events(ir AEs).Hazard Ratio(HR),Odds Ratio(OR),and corresponding 95%confidence interval(CI)of outcomes were calculated.Results: 1.A total of 5944 patients from 10 RCTs were included: four were studies on PD-1/PD-L1 inhibitor monotherapy(n=2652),and six were clinical trials for PD-1/PD-L1 inhibitor plus chemotherapy(n=3292).2.PD-1/PD-L1 inhibitor plus chemotherapy significantly improved PFS(HR=0.61,95% CI 0.55-0.67,P<0.00001),OS(HR=0.71,95% CI 0.58-0.87,P=0.001),ORR(RR=1.59,95% CI 1.32-1.91,P<0.00001),and PD-1/PD-L1 inhibitor monotherapy significantly prolonged OS(HR=0.82,95% CI 0.70-0.97,P=0.02)in comparison to chemotherapy in advanced non-small cell lung cancer(NSCLC).3.In PD-L1≥50% expression levels subpopulation,PD-1/PD-L1 inhibitor monotherapy or plus chemotherapy resulted in better PFS and OS,and PD-1/PDL1 inhibitor plus chemotherapy significantly improved ORR than chemotherapy.In PD-L1≥1%,and <1% expression levels subpopulation,PD-1/PD-L1 inhibitor plus chemotherapy had a significant improvement of PFS,OS,and ORR.PD-1/PD-L1 inhibitors demonstrated higher OS at PD-L1≥1%expression levels.4.In terms of summary adverse events,PD-1/PD-L1 inhibitor monotherapy had a lower incidence of TRAEs and a higher incidence of ir AEs than chemotherapy.PD-1/PD-L1 inhibitor combined with chemotherapy groups had a significant higher risks in TRAEs and ir AEs than chemotherapy.Conclusion: 1.PD-1/PD-L1 inhibitors plus chemotherapy significantly improved survival and regardless of the PD-L1 expression level in the first-line treatment of NSCLC,moreover,the higher PD-L1 expression level,the better efficacy.2.PD-1/PD-L1 inhibitor monotherapy therapy as first-line treatment for advanced NSCLC is significantly better than chemotherapy in patients at PD-L1≥1% expression level,especially at PD-L1≥50%.3.PD-1/PD-L1 inhibitors had a significantly higher risk of ir AEs than chemotherapy,especially 3-5 grade IRAEs in thyroid gland,lung,skin,and alimentary system.