Efficacy and safety of durvalumab with or without tremelimumab in the treatment of metastatic non–small cell lung cancer: a meta-analysis of randomized controlled trials

BACKGROUND: The therapeutic role of combining PD-L1 and CTLA-4 blockade in metastatic non-small cell lung cancer (NSCLC) remains unclear, with individual trials yielding discrepant results. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and safety of durvalumab with or without tremelimumab in advanced NSCLC. The primary outcome was overall survival. Secondary outcomes included immune-related adverse events. Hazard ratios (HRs) and odds ratios with 95% confidence intervals (CIs) were pooled using random- or fixed-effects models according to heterogeneity. RESULTS: Three RCTs (MYSTIC, ARCTIC, and POSEIDON) enrolling 2726 patients met inclusion criteria. Combined analysis showed no significant overall survival benefit with durvalumab plus tremelimumab compared to durvalumab alone (HR 0.97; 95% CI, 0.74-1.27). Pooled analysis of immune-related adverse events demonstrated significantly higher risks in the tremelimumab-containing arms. CONCLUSIONS: In metastatic NSCLC, the addition of tremelimumab to durvalumab does not confer a statistically significant overall survival advantage in unselected populations and is associated with a marked increase in immune-mediated toxicities. Benefits may be restricted to biomarker-defined subgroups, but these findings remain exploratory. Further prospective studies are needed to clarify the optimal role of CTLA-4 blockade in combination immunotherapy.