From biology to therapy: current standards and emerging strategies in pleural mesothelioma

Our plain-English summary of From biology to therapy: current standards and emerging strategies in pleural mesothelioma, by J.H.L.T. van Genugten, C.J. de Gooijer, P. Baas (Frontiers in Oncology, 2026).

The study

• Authors: J.H.L.T. van Genugten, C.J. de Gooijer, P. Baas
• Journal: Frontiers in Oncology
• Published: 2026;16:1778121
• Type of article: Review
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) is an aggressive malignancy with limited therapeutic options and poor long-term prognosis. Platinum-based chemotherapy has been the standard-of-care for most patients for decades. While the decoding of the genomic alterations in PM has triggered renewed interest in mesothelioma biology and targeted therapies, these have yet to reach clinical practice. The recent introduction of dual immune checkpoint blockade (ICB) with nivolumab plus ipilimumab has marked the first major advance in PM treatment for decades, yet, many patients do not respond to these drugs and durable long-term responses remain rare. A range of alternative treatment modalities are currently under clinical investigation in PM, including antibody-drug conjugates, bi-specific antibodies, chimeric antigen receptor T-cells, cancer vaccines, and oncolytic viruses. Here we review recent progress in the understanding of PM biology and evaluate relevant phase I-III clinical trials aimed at improving treatment for this disease. We also highlight ongoing and future clinical trials with promising candidates for PM therapy.

Copyright © 2026 van Genugten, de Gooijer and Baas.

In plain English

This was a narrative review, not a new study, of the biology and treatment of pleural mesothelioma. The authors searched PubMed for clinical trials published between January 2020 and October 2025 and screened clinicaltrials.gov for ongoing trials. In background, they described the cancer as associated with inhaling asbestos fibres, without naming fiber types. Among the trials reviewed, Vogelzang and colleagues (2003) reported median survival of 12.1 months with pemetrexed plus cisplatin versus 9.3 months with cisplatin alone. The CheckMate 743 trial reported median survival of 18.1 months with nivolumab plus ipilimumab versus 14.1 months with chemotherapy. Gains were larger in the non-epithelioid subtype, although that trial was not powered for subgroup analysis. In that trial, serious treatment-related side effects occurred in 21% of immunotherapy patients and 8% of chemotherapy patients. Newer approaches generally showed acceptable safety but modest effect in early trials. The authors concluded that there remains a clear unmet need for better therapies and that single-agent first-line immunotherapy should be discouraged.

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: Narrative review of pleural mesothelioma biology and clinical trials of treatments
• Who was studied: Published phase I to III clinical trials in pleural mesothelioma identified through PubMed (January 2020 to October 2025), plus earlier relevant articles and ongoing trials listed on clinicaltrials.gov
• Exposure: Treatments studied in the reviewed trials: chemotherapy, immune checkpoint blockade, anti-angiogenic drugs, targeted therapies, antibody-drug conjugates, bi-specific antibodies, CAR-T cells, vaccines and oncolytic viruses. Asbestos is discussed only as background: the authors describe the disease as associated with inhalation of asbestos fibres, without naming fiber types.
• Main results:
  • Vogelzang et al. (2003) trial, as reviewed: median overall survival 12.1 months with pemetrexed plus cisplatin vs 9.3 months with cisplatin alone (HR 0.77, log-rank p = 0.020)
  • CheckMate 743 trial, as reviewed: median overall survival 18.1 months with ipilimumab plus nivolumab vs 14.1 months with chemotherapy (HR 0.74, p = 0.0020)
  • CheckMate 743 subgroup: in the non-epithelioid subtype, median overall survival rose from 8.8 months on chemotherapy to 18.1 months on immune checkpoint blockade. The trial was not powered for subgroup analysis.
  • CheckMate 743: serious treatment-related adverse events in 21% of patients on nivolumab plus ipilimumab and 8% of patients on platinum-based chemotherapy
  • BEAT-meso trial: in patients with the non-epithelioid subtype, adding bevacizumab improved progression-free survival (HR 0.43, p < 0.001) and overall survival (HR 0.50, p = 0.0022). The overall survival gain in all patients (18.1 to 20.5 months) was not significant.
  • PEMMELA trial: pembrolizumab plus lenvatinib gave a 58% response rate in patients who progressed after chemotherapy (n = 38) and 60% in patients who progressed after first-line nivolumab plus ipilimumab (n = 20)
  • Single-agent angiogenesis inhibitors (cediranib, vatalanib, sunitinib, nintedanib) produced responses between 0 and 9%
  • Newer treatment types tested in phase I/II studies generally showed acceptable safety, but the authors described their efficacy as modest
• The authors' conclusion: The authors concluded that there remains a clear unmet need for improved therapies, and that, based on phase III trials, single-agent first-line immunotherapy should be discouraged because its efficacy is limited.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Chemotherapy, Mesothelioma, Nivolumab (Opdivo), Ipilimumab (Yervoy), Clinical Trial.

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