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.
Visani et al. (Thu,) studied this question.