Targeted agents combined with immune checkpoint inhibitors in advanced non-small cell lung cancer: a systematic review and externally anchored Bayesian network meta-analysis
Year: 2026
Type: article
Study designs: Systematic Review, Meta-Analysis
Abstract: Background: Combining targeted therapies with immune checkpoint inhibitors (ICIs) represents a promising strategy for the treatment of advanced non-small cell lung cancer (NSCLC), particularly in molecularly defined subgroups. However, the absence of randomized head-to-head trials comparing different targeted–immunotherapy combinations limits definitive conclusions about their relative efficacy. Objective: We performed an exploratory Bayesian network meta-analysis (NMA) of single-arm studies to generate model-based estimates of efficacy for three clinically relevant targeted–immunotherapy combination classes in advanced NSCLC: EGFR inhibitor (EGFRi) + PD-1 inhibitor, EGFRi + PD-L1 inhibitor, and multitarget tyrosine kinase inhibitor (MTKI) + PD-1 inhibitor, using platinum-based chemotherapy as a contextual external benchmark. Method: A systematic search of PubMed, Embase, and the Cochrane Library was conducted up to 30 March 2025. Twenty-six eligible single-arm studies involving 1,638 patients were identified. Primary outcomes were objective response rate (ORR) and median progression-free survival (mPFS). A Bayesian hierarchical model was applied, with platinum-based chemotherapy from authoritative phase III trials serving as a contextual virtual comparator. Results: EGFRi + PD-L1 showed the highest model-based posterior mean ORR (approximately 60%), followed by chemotherapy (approximately 35%), MTKI + PD-1 (approximately 31%), and EGFRi + PD-1 (approximately 23%). Compared with the chemotherapy benchmark, EGFRi + PD-L1 showed a numerically higher model-based odds ratio (OR = 2.93; 95% credible interval [CrI]: 1.10–7.82), while EGFRi + PD-1 showed a lower estimate (OR = 0.56; 95% CrI: 0.18–1.71). Safety data were heterogeneously reported and are presented descriptively only. Conclusions: In this exploratory Bayesian synthesis, EGFRi + PD-L1 showed numerically higher model-based efficacy estimates, MTKI + PD-1 showed intermediate estimates, and EGFRi + PD-1 showed the lowest model-based efficacy estimates. Given the inherent limitations of single-arm evidence synthesis and the use of a contextual external comparator, these findings are hypothesis-generating and should not be interpreted as definitive comparative effectiveness conclusions. Prospective randomized trials are needed to confirm these signals.
Source: BMC Cancer
Authors: Jianxiong Kang, Jianhong Zhou, Shenjie Yang
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,390
OpenAlex ID: W7212119771