The efficacy and safety of immune-checkpoint inhibitors plus chemotherapy versus chemotherapy for non-small cell lung cancer: An updated systematic review and meta-analysis

Background Immune-checkpoint inhibitors(ICIs) combined with chemotherapy are emerging as an effective first-line treatment in advanced non-small cell lung cancer (NSCLC); however, reports on the magnitude of effectiveness and safety are conflicting. Methods Relevant articles published before February 2022 were searched in PubMed, Embase, and the Cochrane Library. The study included all randomized controlled trials that evaluated ICIs with chemotherapy versus chemotherapy for the treatment of NSCLC. Among the outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Results Our meta-analysis included a total of 12 studies. Overall analysis indicated that ICIs plus chemotherapy could significantly improve OS (HR = 0.79; 95% CI: 0.74–0.84; I 2 = 44.4%, P = 0.055), PFS (HR = 0.62; 95% CI: 0.59–0.67; I 2 = 75.3%, P = 0.000), and ORR (RR = 1.48; 95% CI: 1.27–1.73; I 2 = 79.0%, P = 0.000) when compared to chemotherapy treatments. Subgroup analysis showed that PD-1/PD-L1 inhibitors combined with chemotherapy significantly improved OS, PFS, and ORR when compared with chemotherapy with decreased grade 1–2 TRAEs. In addition, female patients with nonsquamous histology might receive more OS benefit from ICIs plus chemotherapy when compared to chemotherapy alone. Despite the fact that CTLA-4 inhibitors combined with chemotherapy increased PFS, there were no benefits gained in OS nor ORR. When PD-L1/CTLA-4 inhibitors were added to chemotherapy, the risk of grade 3–5 adverse events increased whereas PD-1 inhibitors did not. Conclusions ICIs plus chemotherapy, compared with chemotherapy, were associated with significantly improved PFS, ORR, and OS in NSCLC therapy. However, PD-L1/CTLA-4 inhibitors plus chemotherapy could increase the risk of grade 3–5 adverse events, but not PD-1 inhibitors plus chemotherapy.