Safety evaluation of PD-1/PD-L1 therapies for treatment of NSCLC: a systematic review, bayesian network meta-analysis, and cost-effectiveness analysis.

BACKGROUND: Lung cancer remains the foremost cause of cancer-related mortality worldwide. With the expanding use of PD-1/PD-L1 inhibitors in its treatment, a comprehensive understanding of their safety profiles and economic implications is essential to guide clinical decision-making. OBJECTIVE: This study evaluates the safety and economics of PD-1/PD-L1 inhibitors in NSCLC. Our findings indicate that they are a cost-effective option with a favorable benefit-risk profile, offering practical guidance for immunotherapy decisions. METHODS: We have conducted a comprehensive literature search for randomized controlled trials (RCTs) evaluating PD-1/PD-L1 inhibitors in PubMed, Web of Science, and the Cochrane Library up to August 2025. Eligible studies were limited to English-language RCTs relevant to network meta-analysis (NMA). This systematic review and NMA was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data extraction was carried out independently by two investigators. The data were then synthesized using a Bayesian random-effects model for NMA. The primary outcome was the incidence of immune-related adverse events, which was analyzed and compared across different PD-1/PD-L1 inhibitor regimens. RESULTS: A total of 60 eligible articles were involved, covering 13 treatments and 23,992participants. The safety evaluation revealed significant differences in toxicity profiles among PD-1/PD-L1 inhibitors, highlighting treatment-specific adverse effect patterns. Based on disability-adjusted life years (DALYs), the pharmacoeconomic analysis identified pembrolizumab as a dominant therapeutic strategy. CONCLUSIONS: Among the evaluated regimens, nivolumab plus ipilimumab was associated with the broadest toxicity spectrum. Sintilimab demonstrated a more favorable safety profile than other PD-1/PD-L1 inhibitors and ranked highest in the safety assessment.Our pharmacoeconomic analysis identified pembrolizumab as the most cost-effective option across treatment lines for NSCLC. The protocol was registered in advance in PROSPERO online platform as CRD42023442502.