Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in the treatment of diffuse pleural mesothelioma: a systematic review and meta-analysis

Our plain-English summary of Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in the treatment of diffuse pleural mesothelioma: a systematic review and meta-analysis, by P. Sun, D. Song, N. Ma, et al (Frontiers in Immunology, 2025).

The study

• Authors: P. Sun, D. Song, N. Ma, S. Hou, L. Liu, J. Gao, Y. Tian
• Journal: Frontiers in Immunology
• Published: 2025;16:1578746
• Type of article: Systematic review, Meta-analysis
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: While clinical trials confirm the therapeutic value of PD-1/PD-L1 and CTLA-4 inhibitors in diffuse pleural mesothelioma, their real-world safety and efficacy profiles remain incompletely defined. This meta-analysis synthesizes clinical evidence to comprehensively evaluate these outcomes, addressing an urgent need for robust real-world evidence.

Methods: PubMed, Embase, the Cochrane Library were systematically searched for relevant studies. Outcomes including median progression-free survival (mPFS), median overall survival (mOS), 1-year overall survival (1-y OS), 1 year progression-free survival (1-year PFS),objective response rate (ORR), disease control rate (DCR), complete response(CR),partial response (PR), stable disease(SD), progressive disease(PD), treatment-related adverse events (TRAEs) and ≥grade 3 TRAEs were extracted for further analysis. The risk of bias was assessed by subgroup analysis.

Results: 14 articles with 1345 patients were identified and subjected to meta-analysis. With regard to survival analysis, the pooled mOS and mPFS were 6.66 months (95%CI 4.85-9.16) and 2.92 months (95%CI 2.23-3.83), respectively. In terms of tumor response, the pooled ORR and DCR were 21% (95%CI 6%-41%) and 49% (95%CI 27%-71%), respectively. The pooled AEs rate and ≥ grade 3 AEs rate were 94% (95%CI 86%-99%) and 44% (95%CI 30%-58%).

Conclusion: PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors have shown effective clinical responses in the treatment of Diffuse Pleural Mesothelioma (DPM). Although the incidence of adverse reactions is high, they are generally tolerable.

Systematic Review Registration: www.inplasy.com, identifier INPLASY202520045.

Copyright © 2025 Sun, Song, Ma, Hou, Liu, Gao and Tian.

In plain English

This systematic review and meta-analysis pooled results from earlier published studies and collected no new patient data. The authors searched PubMed, Embase and the Cochrane Library to November 30, 2024 for studies of diffuse pleural mesothelioma treated with a PD-1 or PD-L1 blocker plus a CTLA-4 blocker, mostly nivolumab plus ipilimumab. They pooled 13 articles covering 14 patient groups and 1,345 patients; asbestos exposure was not studied. In the main text, pooled median overall survival was 15.17 months (95% CI 11.25 to 19.09) and median progression-free survival 5.84 months (95% CI 4.20 to 7.48). Pooled one-year survival was 60% (95% CI 53% to 67%) and objective response 27% (95% CI 22% to 32%). Any-grade treatment-related side effects had a pooled rate of 75% (95% CI 64% to 87%), and grade 3 or higher 28% (95% CI 22% to 34%). The abstract reports different, unexplained figures, such as 6.66 months survival. The authors concluded the combination gave clinically meaningful survival benefits with acceptable safety, noting that most studies were small and that they relied on published summary data.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Systematic review and meta-analysis of published studies; all included studies were treated as non-randomized
• Who was studied: 13 articles (14 cohorts) with a total of 1,345 adults with diffuse pleural mesothelioma, found in Cochrane Library, Embase and PubMed through November 30, 2024. The cohorts came from the Netherlands, France, Italy, the USA, Japan, Switzerland, Australia and multinational trials.
• Exposure: Treatment with PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors, with or without other standard treatments: nivolumab plus ipilimumab in most cohorts, and durvalumab plus tremelimumab in two cohorts. Asbestos exposure was not studied.
• Main results:
  • Pooled median overall survival: 15.17 months (95% CI 11.25 to 19.09), from six studies with 732 patients
  • Pooled median progression-free survival: 5.84 months (95% CI 4.20 to 7.48), from 944 patients in 8 studies
  • Pooled 1-year overall survival rate: 60% (95% CI 53% to 67%), from nine trials with 909 patients
  • Pooled 1-year progression-free survival rate: 29% (95% CI 24% to 34%), from four trials with 446 patients
  • Pooled objective response rate: 27% (95% CI 22% to 32%), from twelve trials with 1,300 patients
  • Pooled disease control rate: 64% (95% CI 56% to 71%), from 12 studies with 1,182 patients (printed as 'DRR')
  • Pooled rate of treatment-related adverse events of any grade: 75% (95% CI 64% to 87%), from 10 studies, with high between-study heterogeneity (I2 = 96.9%)
  • Pooled rate of grade 3 or higher treatment-related adverse events: 28% (95% CI 22% to 34%), from 12 studies, with high between-study heterogeneity (I2 = 81.9%)
  • In subgroup analysis, cohorts given first-line treatment (3 studies) had a pooled median overall survival of 17.98 months (95% CI 13.64 to 22.31)
  • Prospective studies showed higher pooled rates than retrospective studies of any-grade adverse events (88% vs. 60%) and of grade 3 or higher adverse events (32% vs. 23%)
• The authors' conclusion: The authors concluded that dual PD-1/PD-L1 and CTLA-4 blockade provides clinically meaningful survival benefits with acceptable safety in diffuse pleural mesothelioma. They also called for future research on biomarkers to identify the patients most likely to benefit.
• Limitations the authors state:
  • Most included studies had small samples, which limited statistical power for subgroup analyses
  • The analysis used aggregated published data rather than individual patient data, which may introduce bias
  • Differences in prior therapies, dosing schedules and patient comorbidities may confound the first-line versus later-line comparisons
  • There was no biomarker-based stratification of patients (for example PD-L1 expression or tumor mutational burden)
  • Limited reporting by histological subtype made meta-regression impossible

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: PD-1/PD-L1, CTLA-4, checkpoint inhibitors, Pleural Mesothelioma, Systematic Review, Meta-Analysis, Clinical Trial, Progression-Free Survival.

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