Comparative efficacy and safety of first-line PD-1/PD-L1 inhibitors in immunotherapy for non-small cell lung cancer: A network meta-analysis

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The emergence of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors offers new therapeutic options for patients with advanced NSCLC, but a comprehensive evaluation of their efficacy and safety is still lacking. In the present study randomized controlled trials (RCTs) published from January 2005 to May 2023 were identified through searches of PubMed, the Cochrane Library and Embase. Analysis focused on 10 PD-1/PD-L1 inhibitors for stages III and IV NSCLC in studies evaluating overall survival (OS), progression-free survival (PFS), the objective response rate, the disease control rate (DCR) and the incidence of severe treatment-related and immune-related adverse events. A total of 37 RCTs involving 31,779 patients were included in the analysis. Compared with chemotherapy, tislelizumab, pembrolizumab and nivolumab all significantly improved OS, with tislelizumab showing the highest probability of being the best treatment for improving OS and DCR. While cemiplimab and tislelizumab had the highest probabilities of improved PFS, no significant differences were observed across all PD-1/PD-L1 inhibitors. Combination therapies, such as nivolumab or cemiplimab with chemotherapy, increased OS and PFS but also increased the incidence of severe treatment-related adverse events. In particular, cemiplimab and pembrolizumab were associated with a greater risk of severe immune-related adverse events. In conclusion, PD-1/PD-L1 inhibitors, especially tislelizumab, pembrolizumab and nivolumab, were effective first-line treatments for NSCLC, providing survival benefits. However, the combination of PD-1/PD-L1 inhibitors with chemotherapy increased the risk of severe adverse events. Further research is needed to optimize treatment strategies.