Abstract Rationale Pleural mesothelioma is an aggressive malignancy arising from the pleural lining, with limited therapeutic options and poor prognosis. The cisplatin-pemetrexed regimen has long been the standard first-line therapy for unresectable disease, offering only modest survival benefits. Nivolumab plus ipilimumab demonstrated better survival rates compared to chemotherapy in the CheckMate 743 trial and has been approved by the FDA for first-line treatment. However, real-world data of this combination remain limited and scattered across heterogeneous studies. This meta-analysis aims to provide an updated evaluation of the efficacy and safety of nivolumab plus ipilimumab in the management of pleural mesothelioma. Methods We systematically searched PubMed, Embase, Cochrane Library, and Google Scholar databases from inception to September 2025 to identify relevant studies. Our primary outcomes were the median overall survival (mOS), median progression-free survival (mPFS), 1-year overall survival (1-y OS), 1 year progression-free survival (1-year PFS), objective response rate (ORR), and disease control rate (DCR). The secondary outcome was treatment-related adverse events (TRAEs). Data extraction and quality assessment were performed independently by two reviewers. Pooled analyses were conducted using a random-effects model, and results were reported as pooled estimates with 95% confidence intervals (CIs). All statistical analyses were performed using RStudio. Results A total of 12 studies, including 4 randomized controlled trials, were analyzed. Dual immune checkpoint inhibition with nivolumab and ipilimumab significantly improved survival, with mOS increased by 14.59 months (95% CI: 10.62-18.55, p 0.0001, I2=89.9%) and mPFS 5.63 months (95% CI: 4.03-7.23, p 0.0001, I2=94%). 1-year OS was 61% (95% CI: 52%-69%, p 0.0001, I2=78%), while 1-year PFS showed no significant improvement (0.29, 95% CI: 0.24-0.35, p = 0.1919, I2=39.4%). Among response outcomes, ORR was 26% (95% CI: 22%-31%, p 0.0001, I2=77.5%) and DCR was 63% (95% CI: 55%-70%, p 0.0001, I2=87%). TRAEs occurred in 71% of cases (95% CI: 54%-87%, p 0.0001, I2=98.6%). Given the high heterogeneity, sensitivity analyses were performed using a leave-one-out approach. Excluding individual studies did not materially alter the direction or significance of pooled outcomes, confirming the reliability and consistency of the overall estimates. Subgroup analyses by study type and treatment line confirmed consistent survival benefits across patient populations, supporting the robustness of these findings. Conclusion Dual immune checkpoint inhibition with nivolumab and ipilimumab significantly improves survival and tumor response in pleural mesothelioma. Despite consistent outcomes across subgroups, the high incidence of treatment-related adverse events is concerning and reinforces careful patient selection and vigilant toxicity monitoring during the therapy. This abstract is funded by: None
Chahodiya et al. (Fri,) studied this question.