C31-12 Efficacy and Safety of Pembrolizumab in Treating Pleural Mesothelioma: A Network Meta-Analysis of Randomized Controlled Trials

Rationale Pleural mesothelioma is a rare, aggressive malignancy primarily caused by asbestos exposure. Conventional chemotherapy provides limited survival benefit, with most patients progressing within months. Pembrolizumab, a PD-1 inhibitor, has shown encouraging activity, and its combination with chemotherapy may further improve outcomes. This network meta-analysis compared the efficacy and safety of pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy alone in patients with pleural mesothelioma. Methods A systematic search was performed using PubMed, Scopus and Cochrane databases for relevant randomized controlled trials (RCTs) published up to 2 November 2025. Eligible trials were assessed with Cochrane RoB2.0. Hazard ratios (HRs) and relative risks (RRs) were generated using R v.4.5.2. The outcomes of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events [AEs] were analyzed. Results Four trials comprising 679 patients with pleural mesothelioma were analyzed. Pembrolizumab plus chemotherapy, but not pembrolizumab alone, demonstrated a significant benefit over chemotherapy (HR 0.79 [95% CI 0.66-0.95]). PFS also improved with pembrolizumab plus chemotherapy compared with chemotherapy alone (HR 0.79 [0.65-0.96]), whereas pembrolizumab alone did not show a statistically significant effect. Patients receiving pembrolizumab plus chemotherapy were nearly two-times more likely to achieve a favorable response (RR 1.93 [0.44-8.34]; I²=62%). The risk of any-grade AEs was slightly higher with pembrolizumab plus chemotherapy (RR 1.14 [1.05-1.24]; I²=0%), while grade ≥3 AEs and treatment-related deaths were comparable across regimens, though heterogeneity was high (I² = 86% for grade ≥3 AEs; not available for deaths). Conclusion Pembrolizumab plus chemotherapy significantly improves survival and disease control in pleural mesothelioma with acceptable toxicity, supporting its potential as a frontline regimen. Pembrolizumab monotherapy provides limited efficacy and may be reserved for select patients. Larger RCTs are warranted to refine patient selection and confirm long-term outcomes. This abstract is funded by: None