Comparative efficacy of immune checkpoint inhibitor–anti-VEGF inhibitor combinations in non–small cell lung carcinoma: A network meta-analysis of randomized trials.

Abstract

e20629 Background: Concomitant inhibition of the vascular endothelial growth factor (VEGF) pathway together with PD-1 or PD-L1 immune checkpoint blockade has demonstrated synergistic activity in non-small cell lung cancer (NSCLC). However, comparative evidence across individual immune checkpoint inhibitor (ICI) and anti-VEGF combinations remains limited. This network meta-analysis (NMA) aimed to evaluate and compare the efficacy of available ICI plus anti-VEGF combination strategies in NSCLC. Methods: A systematic search of three electronic databases and two clinical trial registries was conducted to identify randomized controlled trials evaluating combinations of ICIs with anti-VEGF agents. A frequentist NMA framework was applied using the netmeta package in R. Hazard ratios (HRs) were used for overall survival (OS) and progression-free survival (PFS), while odds ratios (ORs) were used for objective response rate (ORR). Treatment ranking was performed using P scores. Results: A total of 24 randomized controlled trials were included in the network. For survival outcomes, the combination of nivolumab plus bevacizumab demonstrated significantly improved OS (HR = 0.66, 95% CI 0.50–0.88) and PFS (HR = 0.46, 95% CI 0.27–0.81) compared with standard chemotherapy. In addition, atezolizumab plus bevacizumab was associated with a significant OS benefit over chemotherapy (HR = 0.79, 95% CI 0.65–0.95). Indirect comparisons showed that nivolumab plus bevacizumab significantly improved PFS compared with pembrolizumab monotherapy, as well as pembrolizumab combined with lenvatinib or chemotherapy. Furthermore, nivolumab combined with sitravatinib demonstrated significantly superior OS and PFS compared with ramucirumab and chemotherapy. For ORR assessed using RECIST 1.1, nivolumab-based combinations could not be incorporated into the network due to insufficient data, and no other combination demonstrated a statistically significant advantage over chemotherapy. However, indirect comparisons showed that pembrolizumab plus lenvatinib was superior to lenvatinib monotherapy (OR = 4.76, 95% CI 1.04–25.0). P-score rankings identified nivolumab plus bevacizumab as the top-ranked regimen for survival outcomes, followed by atezolizumab plus bevacizumab. For ORR, pembrolizumab plus lenvatinib ranked highest, followed by atezolizumab plus bevacizumab. Conclusions: Nivolumab-based ICI and anti-VEGF combinations, particularly with bevacizumab and sitravatinib, demonstrate the most favorable survival outcomes in NSCLC. Evidence for ORR remains limited, and further randomized comparisons are required to better define the relative efficacy of these combinations.