Efficacy and safety of immune checkpoint inhibitors after platinum-based therapy for refractory or recurrent malignant pleural mesothelioma: A systematic review and meta-analysis.

Abstract

e20064 Background: Malignant pleural mesothelioma (MPM) remains highly aggressive. While immune checkpoint inhibitors (ICIs) are established in first-line therapy, their efficacy in the refractory setting, followed by platinum-based doublet chemotherapy (CT) failure, remains uncertain. Hence, this systematic review and meta-analysis aim to evaluate the clinical benefit of ICIs for recurrent malignment mesothelioma after platinum based therapy. Methods: We systematically searched PubMed, Embase, and Cochrane for studies of ICIs in adults with MPM progressing after platinum-based CT. Studies including treatment-naïve patients, potentially resectable disease, or non-isolable combination therapies were excluded. We compared monotherapy and doublet ICIs regimens and performed subgroup analysis based on the therapeutic class combinations (anti-PDL1, anti-CTLA4, anti-PD1). The outcomes of interest were progression free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (TRAEs). All the statistical analyses were performed in R version 5.3 using a random-effects model and meta-analysis of proportions, with heterogeneity assessed via I² statistics and Cochran’s Q test. Results: Among 1.220 screened studies, 13 met the inclusion criteria, representing 1.014 patients with recurrent MPM treated with ICIs. The 1-year OS was 60.4% (95% CI, 50.3–69.7; I² = 0%) for studies with doublet ICIs and 45.9% (95% CI, 41.9–49.9; I² = 0%) for studies utilizing monotherapy (p value for subgroup difference = 0.009). The pooled 1-year PFS was 17.1% (95% CI, 11.6–24.4; I² = 0%). ORR were 25.3% (95% CI, 17.1–35.7; I² = 49.8%) in doublet ICIs studies and 11% (95% CI, 6.7–17.5; I² = 79.9%) in monotherapy (p= 0.0072). Stratified by class, anti-PD1 plus anti-CTLA4 shows an ORR of 25.4%, anti-PD1 of 16.6%, and anti-CTLA4 of 4.7% (p=0.0001). Disease control rates were 58.6%, 51.7%, and 28.0%, respectively (p = 0.0001). Any-grade TRAEs occurred in 93.7% (95% CI, 86.7–97.1; I² = 0%) of patients receiving doublet therapy and 70.5% (95% CI, 61.2–78.3; I² = 81%) of those receiving monotherapy (p = 0.0001), with grade ≥3 TRAEs reported in 23.4% of patients and treatment discontinuation in 10.8%. Conclusions: ICIs demonstrate clinical activity in patients with MPM previously exposed to chemotherapy, particularly in combination regimens, albeit with a toxicity burden. However, randomized clinical trials are needed to confirm these findings, define the optimal therapeutic strategy, and refine patient selection in this setting.