Indirect Comparison Between Immune Checkpoint Inhibitors And Immune Checkpoint Inhibitors Plus Chemotherapy As First-line Treatment For Advanced Non-small Cell Lung Cancer:A Systematic Review

Objectives: The choice of immune checkpoint inhibitors(ICIs)as first-line treatment for advanced non-small cell lung cancer(NSCLC)remains controversial.Because of the lack of clinical trials comparing single-drug ICIs with ICIs plus chemotherapy,this systematic review aimed to indirectly compare ICIs alone with ICIs plus chemotherapy as first-line treatment for advanced NSCLC.Methods: We systematically searched PubMed,the Cochrane Library,Embase,and ClinicalTrials.gov.We also collected relevant conference abstracts.Review Manager 5.3 software was used to analyze the efficacy and safety of single-drug ICIs versus chemotherapy and ICIs plus chemotherapy versus chemotherapy for first-line treatment of advanced NSCLC.Indirect comparison was conducted using chemotherapy as the common therapeutic arm.ITC 1.0 software was used to compare the data indirectly,and Stata 12.0 software was used for publication bias and sensitivity analysis.The following main outcomes were analyzed: progression-free survival(PFS),overall survival(OS),objective response rate(ORR),and incidence of related adverse events.Hazard ratio(HR)and risk ratios(RR)were used as value indices of effects.We also calculated the 95% confidence intervals(95% CI)of the corresponding indicators.We registered this study in the PROSPERO international register of systematic reviews(CRD 42018116589).Results: Ten randomized controlled clinical trials(n = 5842)were included: three were studies on ICIs alone(n = 2120),and seven were clinical trials for ICIs plus chemotherapy(n = 3722).ICIs plus chemotherapy as first-line treatment for advanced NSCLC had a tendency to improve PFS,OS,and ORR compared with ICIs alone;however,the differences were not statistically significant.When tumor programmed death ligand 1(PD-L1)expression was at least 50%,ICIs plus chemotherapy improved PFS compared with ICIs alone as first-line treatment for advanced NSCLC,the difference was statistically significant(HR=1.95;95% CI 1.27-3.00).ICIs plus chemotherapy had a tendency to prolong OS compared with ICIs alone,but the difference was not statistically significant(HR=1.48;95% CI 0.90-2.42).When PD-L1 expression was at least 1%,for first-line treatment of advanced NSCLC,ICIs plus chemotherapy improved PFS(HR=2.14;95% CI 1.81-2.53)and OS(HR=1.67;95% CI 1.12-2.50)compared with ICIs alone,the difference was statistically significant.The incidence of treatment-related adverse events for ICIs alone as first-line treatment for advanced NSCLC was less than that for ICIs plus chemotherapy.Meanwhile,the incidence of immune-related adverse events for ICIs alone as first-line treatment for advanced NSCLC was higher than that for ICIs plus chemotherapy.The outcomes for adverse events showed that the differences were statistically significant.Conclusions: The results of this study are that there is no significant difference in OS,PFS and ORR between ICIs alone and ICIs plus chemotherapy as first-line treatment for advanced NSCLC.ICIs plus chemotherapy as first-line treatment for advanced NSCLC is significantly better than ICIs alone in patients with PD-L1 expression in ≥50% and ≥1% of tumor cells.At the same time,the incidence of immune-related adverse events in ICIs plus chemotherapy is relatively less than that in ICIs alone,and the difference is statistically significant.