Meta-Analysis on the Combination of Chemotherapy With Programmed Death-Ligand 1 and Programmed Cell Death Protein 1 Blockade as First-Line Treatment for Unresectable Pleural Mesothelioma

Background Dual immune checkpoint blockers (ICBs) regimen represents a standard first-line therapy in unresectable pleural mesothelioma (PM). Novel combination strategies, including ICBs and antiangiogenic drugs, are currently under investigation in this setting. We aimed to assess the efficacy of chemo-immunotherapy combination by reference of literature evidence. Methods A systematic review and meta-analysis of trials with first-line platinum-based chemotherapy associated with anti-PD(L)1 agents in unresectable PM. We estimated weighted summary proportion of disease response, along with landmark probability of survival outcomes. Results 349 patients with unresectable PM from four trials (DREAM, PrE0505, JME-001, IND.227) were included, 79% (n=274) with epithelioid and 21% (n=75) with non-epithelioid histologic type. In aggregate, objective response rate (ORR) was 59.2% (95%CI: 50.3%-67.9%) and disease control rate (DCR) was 92.2% (95%CI: 89.2%-94.8%). Comparing epithelioid vs. non-epithelioid tumors, the ORR was 64.5% vs. 46.4%, (p<0.001) and the DCR was 92.3% vs. 80.0%, (p=0.043), with on odds ratio of 2.56 (95%CI: 1.51-4.32) for disease response and of 3.37 (95%CI: 0.99-11.47) for disease control. Aggregated estimated probability of progression-free survival was 63% (95%CI: 53%-71%) at 6 months and 25% (95%CI: 21%-31%) at 12 months, whereas 6-, 12- and 24-month overall survival rates were 88% (95%CI: 81%-93%), 71% (95%CI: 61%-79%) and 39% (95%CI: 34%-45%), respectively. Conclusion According to our analysis, first-line chemo-immunotherapy shows promise as a potential novel treatment approach for PM, exhibiting encouraging survival outcomes and an enhanced response rate, including for the epithelioid subtype. Ongoing studies are necessary to establish its precise placement within the treatment algorithm.