Background Selecting optimal first-line immunotherapy for advanced non‑small cell lung cancer (NSCLC) is challenging, especially with multiple novel agents developed in China. This network meta-analysis (NMA) compares all approved programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitor combinations, focusing on Chinese-developed versus imported agents, to inform treatment selection and healthcare policy. Methods Following NMA guidelines, we systematically searched ClinicalTrials.gov, PubMed/MEDLINE, and oncology conference abstracts up to February 28, 2024, for phase III randomized controlled trials (RCTs) of first-line PD-1/PD-L1 inhibitor combinations in stage III–IV NSCLC. Two investigators extracted data and assessed bias using Cochrane RoB 2.0. Bayesian NMA (fixed-effects model) was performed to synthesize evidence on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Additional NMAs were conducted for grade ≥3 treatment-related adverse events (TRAE) and immune-related adverse events (IrAE). Results Twenty-five RCTs (15,026 patients) evaluating 21 treatment regimens were included. Most combinations outperformed chemotherapy. Penpulimab plus chemotherapy ranked highest for OS (hazard ratio HR: 0.55, 95% confidence interval CI: 0.40–0.75) and ORR (odds ratio OR: 3.1, 95% CI: 2.0–4.9), while nivolumab plus bevacizumab plus chemotherapy had optimal PFS (HR: 2.31, 95% CI: 1.39–3.87). Chinese-developed agents (including penpulimab, camrelizumab and sugemalimab) demonstrated comparable or even superior efficacy with imported inhibitors. Heterogeneity was low (I² < 25%). For safety, atezolizumab plus bevacizumab and chemotherapy had the lowest grade ≥3 TRAE risk (OR = 0.29), followed by nivolumab plus bevacizumab and chemotherapy (OR = 0.37); among Chinese-developed agents, tislelizumab (OR = 0.53) and camrelizumab (OR = 0.58) demonstrated similarly lower risks. For IrAE, durvalumab plus tremelimumab (OR = 0.06) and tislelizumab (OR = 0.10) were most favorable. Conclusion This NMA identifies the Chinese-developed agent penpulimab plus chemotherapy as a leading first-line regimen. PD-L1 expression and histology enable personalized selection. Chinese-developed agents expand effective and potentially more accessible options, with implications for national treatment guidelines, drug accessibility, and value-based oncology policy in China and other healthcare systems.
Yang et al. (Mon,) studied this question.