Immunotherapy vs. Chemotherapy in Subsequent Treatment of Malignant Pleural Mesothelioma: Which Is Better?

Our plain-English summary of Immunotherapy vs. Chemotherapy in Subsequent Treatment of Malignant Pleural Mesothelioma: Which Is Better?, by X. Guo, L. Lin, J. Zhu (Journal of Clinical Medicine, 2023).

The study

• Authors: X. Guo, L. Lin, J. Zhu
• Journal: Journal of Clinical Medicine
• Published: 2023;12(7)
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

(1) Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor arising from the pleural surface. For relapsed MPM, there is no accepted standard of- are for subsequent treatment. Thus, we aimed to compare the efficacy of chemotherapy, targeting drugs, and immune-checkpoint inhibitors (ICIs) as subsequent therapy for relapsed MPM. (2) Methods: The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched several acknowledged databases. Primary outcomes were defined as overall median progressive survival (mPFS) and median overall survival (mOS) in different treatment groups. Secondary outcomes were defined as objective response rate (ORR), the proportion of stable disease (SD), and progressive disease (PD). (3) Results: Ultimately, 43 articles were selected for the meta-analysis. According to the results of a pooled analysis of single-arm studies, ICIs showed a slight advantage in mOS, while chemotherapy showed a slight advantage in mPFS (mOS: 11.2 m vs. 10.39 m and mPFS: 4.42 m vs. 5.08 m for ICIs group and chemotherapy group, respectively). We identified only a few studies that directly compared the efficacy of ICIs with that of chemotherapy, and ICIs did not show significant benefits over chemotherapy based on mOS. (4) Conclusions: Based on current evidence, we considered that immunotherapy might not be superior to chemotherapy as a subsequent therapy for relapsed MPM. Although several studies investigated the efficacy of ICIs, targeting drugs, and chemotherapy in relapsed MPM, there was still no standard of care. Further randomized control trials with consistent criteria and outcomes are recommended to guide subsequent therapy in relapsed MPM and identify patients with certain characteristics that might benefit from such subsequent therapy.

In plain English

This article was a systematic review and meta-analysis, not a new study of patients. The authors searched PubMed, Web of Science and Medline for articles published from 1 January 2000 to 30 December 2021 on second- or third-line drug treatment for previously treated malignant pleural mesothelioma (MPM). They selected 43 articles: mostly single-arm studies, plus five randomized controlled trials and one cohort study. Pooling single-arm studies, median overall survival was 10.39 months (95% CI 8.41 to 12.37) with chemotherapy, 11.20 months (8.54 to 13.86) with immune-checkpoint inhibitors (ICIs) and 7.02 months (5.94 to 8.10) with targeting drugs. Median progression-free survival was 5.08 months (4.05 to 6.10), 4.22 months (3.24 to 5.60; the abstract and discussion say 4.42) and 2.45 months (1.94 to 2.96), respectively. In the few direct comparisons, ICIs did not show a significant overall-survival benefit over chemotherapy. The authors concluded that immunotherapy might not be superior to chemotherapy as later-line therapy, and they called for more randomized trials. They noted that only one trial and one cohort study compared ICIs with chemotherapy directly.

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 (single-arm studies, cohort studies and randomized controlled trials), following PRISMA
• Who was studied: 43 published articles (from PubMed, Web of Science and Medline, published 1 January 2000 to 30 December 2021) on previously treated malignant pleural mesothelioma patients. Most were single-arm studies, five were RCTs and one was a cohort study.
• Exposure: Second- or third-line systemic therapy: chemotherapy (e.g. gemcitabine, vinorelbine, irinotecan), targeting drugs (e.g. sorafenib, dasatinib) and immune-checkpoint inhibitors (e.g. tremelimumab, ipilimumab, nivolumab). The analysis did not study asbestos exposure.
• Main results:
  • Chemotherapy group: pooled median overall survival was 10.39 months (95% CI 8.41 to 12.37), from eleven studies.
  • Chemotherapy group: pooled median progression-free survival was 5.08 months (95% CI 4.05 to 6.10), from eight studies.
  • ICI group: pooled median overall survival was 11.20 months (95% CI 8.54 to 13.86), from eight studies.
  • ICI group: pooled median progression-free survival was 4.22 months (95% CI 3.24 to 5.60), from eleven studies, with very high heterogeneity. The abstract and discussion give this figure as 4.42 months.
  • Targeting-drug group: pooled median overall survival was 7.02 months (95% CI 5.94 to 8.10), from seven studies.
  • Targeting-drug group: pooled median progression-free survival was 2.45 months (95% CI 1.94 to 2.96), from ten studies.
  • In the few studies that compared them directly, ICIs did not show significant benefits over chemotherapy in median overall survival. Targeted therapy showed superior median overall survival compared with placebo (mean difference 5.58, 95% CI 4.31 to 6.85).
  • Pooled objective response rate: 0.11 for chemotherapy, 0.03 for targeting drugs and 0.18 for ICIs.
  • Stable disease rate: 0.51 for chemotherapy (highest) and 0.36 for ICIs (lowest).
  • Progressive disease rate: 0.39 for chemotherapy, 0.46 for targeting drugs and 0.44 for ICIs.
• The authors' conclusion: The authors concluded that ICIs might not be superior to chemotherapy as subsequent therapy in relapsed MPM. They stated that there remains no standard of care and that more randomized trials with consistent criteria and outcomes are needed.
• Limitations the authors state:
  • Most included studies were single-arm studies. Only one RCT and one cohort study compared subsequent ICIs with chemotherapy.
  • The included studies did not use the same outcomes, and potential bias might influence the pooled analysis.
  • The pooled single-arm studies had differing designs, and confounding factors were hard to adjust for.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Chemotherapy, Pleural Mesothelioma, checkpoint inhibitors, Systematic Review, Median Overall Survival, Meta-Analysis.

Related studies

• Real-world outcomes of first-line immunotherapy and subsequent systemic therapies in pleural mesothelioma: a multicenter study in China — B. Tian, B. Sun, et al. (2025)
• Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy — Y. Wang, X. Wang, et al. (2015)
• The issue of studies evaluating biomarkers which predict outcome after pemetrexed-based chemotherapy in malignant pleural mesothelioma — F. Mairinger, C. Vollbrecht, et al. (2013)
• High density and proximity of CD8+ T cells to tumor cells are correlated with better response to nivolumab treatment in metastatic pleural mesothelioma — Y. Yin, R. Sakakibara, et al. (2023)
• Is less also better? A single-institution experience on treatment of early stage Malignant Pleural Mesothelioma — P. Bertoglio, M.C. Ambrogi, et al. (2017)
• Learning from the past to design better trials in second-line treatment for mesothelioma patients — A. Addeo, G.L. Banna, et al. (2018)

Browse more research in Journal of Clinical Medicine, or return to medical research.