Efficacy and safety of immune checkpoint inhibitors in advanced non–small cell lung cancer: A systematic review and meta-analysis of randomized trials.

Abstract

e20621 Background: Immune checkpoint inhibitors (ICIs) are standard first line therapy for advanced non small cell lung cancer (NSCLC), yet the magnitude and consistency of benefit across treatment strategies and agents remain incompletely defined. We conducted a comprehensive meta analysis of randomized trials to quantify survival benefit and evaluate key subgroups. Methods: We systematically searched PubMed, Embase, Cochrane Central, and major oncology conferences through January 2026 for randomized trials comparing first-line PD-1 or PD-L1 inhibitors, alone or combined with chemotherapy, versus platinum-based chemotherapy in advanced NSCLC. Random effects models were used to pool hazard ratios (HRs) for overall survival (OS) and progression free survival (PFS). Risk of bias was assessed using RoB 2, and certainty of evidence was graded using GRADE. Results: Twenty three randomized trials including 11,944 patients were analyzed. ICIs significantly improved OS compared with chemotherapy (pooled HR 0.73, 95% CI 0.68–0.78; I² = 46%), corresponding to a 27% reduction in mortality, with a prediction interval excluding the null. OS benefit was consistent across treatment strategies, with similar effects for ICI plus chemotherapy (HR 0.72) and ICI monotherapy (HR 0.76; interaction p = 0.54). PD-1 inhibitors demonstrated significantly greater OS benefit than PD-L1 inhibitors (HR 0.71 vs 0.81; interaction p = 0.03), although both classes improved survival. Survival benefit was consistent across squamous and non-squamous histologies. ICIs also significantly improved PFS (HR 0.60, 95% CI 0.53–0.67), with greater benefit observed for combination regimens compared with monotherapy. The pooled incidence of any grade immune-related adverse events was 37.3%, with higher rates in combination therapy. Results were robust across sensitivity analyses. Certainty of evidence was high for OS and moderate for PFS. Conclusions: First-line immune checkpoint inhibitors provide substantial and consistent overall survival benefit in advanced NSCLC across treatment strategies and histologies. PD-1 inhibitors appear to confer greater survival benefit than PD-L1 inhibitors, supporting their preferential use when clinically appropriate.