Comparison of Chemotherapy With PD-1/L1 or CTLA-4 Inhibitors Alone Or In Combination In Advanced Or Metastatic Non-Small Cell Lung Cancer: A Meta- Analysis

Abstract Background: In spite of the wide use of immune-checkpoint inhibitors (ICIs) in advanced or metastatic non-small cell lung cancer (NSCLC), whether ICIs or conventional chemotherapy is more effective still remains controversial. This study was conducted to evaluate the efficacy of giving patients programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), or cytotoxic T-lymphocyte protein 4 (CTLA-4) alone or in their combination (PD-1/L1 + CTLA-4) versus simply applying chemotherapy in patients with advanced or metastatic NSCLC.Methods: This meta-analysis was conducted from PubMed, Web of Science, Medline, Embase, and the Cochrane Library up to March 2021 to identify relevant randomized controlled trials (RCTs). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint was adverse events (AEs). Results: The search process has identified 13 studies containing 7918 patients with advanced or metastatic NSCLC. The benefit of PD-1/L1 or CTLA-4 inhibitors alone or in combination compared with chemotherapy for advanced or metastatic NSCLC was elucidated in both overall survival (OS) [HR=0.75, 95%CI (0.70-0.80), P<0.001] and progression-free survival (PFS) [HR=0.83, 95%CI (0.73-0.95), P<0.001]. Sex is another vital factor that affects the efficacy of ICIs. Male [HR=0.71, 95%CI (0.63-0.81)] benefits more from ICIs than the female [HR 0.80, 95%CI (0.68-0.94)] in OS. Besides, ICIs were associated with fewer AEs compared to chemotherapy.Conclusion: PD-1/L1 or CTLA-4 inhibitors alone or in combination, with fewer AEs, was associated with significant improvements in terms of OS and PFS than chemotherapy in treatment of advanced or metastatic NSCLC.