Emerging Treatments for Malignant Pleural Mesothelioma: Where Are We Heading?

Our plain-English summary of Emerging Treatments for Malignant Pleural Mesothelioma: Where Are We Heading?, by L. Cantini, R. Hassan, D.H. Sterman, et al (Frontiers in Oncology, 2020).

The study

• Authors: L. Cantini, R. Hassan, D.H. Sterman, J.G.J.V. Aerts
• Journal: Frontiers in Oncology
• Published: 2020;10:343
• Type of article: Review
• Cited by: 52 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an uncommon but aggressive and treatment resistant neoplasm with low survival rates. In the last years we assisted to an exponential growth in the appreciation of mesothelioma pathobiology, leading several new treatments to be investigated both in the early stage of the disease and in the advanced setting. In particular, expectations are now high that immunotherapy will have a leading role in the next years. However, caution is required as results from phase II studies in MPM were often not replicated in larger, randomized, phase III trials. In this review, we describe the most promising emerging therapies for the treatment of MPM, discussing the biological rationale underlying their development as well as the issues surrounding clinical trial design and proper selection of patients for every treatment.

Copyright © 2020 Cantini, Hassan, Sterman and Aerts.

In plain English

This article is a narrative review, not an original study. Writing in 2020, the authors described emerging treatments for malignant pleural mesothelioma, a cancer whose causal link to airborne asbestos they called well established. They also listed ongoing clinical trials taken from ClinicalTrials.gov. The review covered surgery, radiotherapy and drugs given before or after surgery, chemotherapy, Tumor Treating Fields, anti-angiogenic drugs, targeted therapies, mesothelin-targeted therapies, immune checkpoint inhibitors, vaccines, CAR-T cell therapy and virus-based therapy. It drew on previously reported research, including clinical trials and laboratory, animal and genetic studies. In the cited LUME-meso phase III trial of 458 patients, progression-free survival did not differ between the nintedanib and placebo groups. In the cited PROMISE-meso trial, more patients responded to pembrolizumab than to chemotherapy (22% vs. 6%), but this did not translate into delayed progression or longer survival. The authors noted that phase II results were often not replicated in larger randomized phase III trials. They described the evidence for checkpoint inhibitors as still incomplete. They concluded that validated biomarkers to select patients, and well-designed, biomarker-driven trials, are needed.

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 emerging therapies for malignant pleural mesothelioma, with a table of ongoing trials
• Who was studied: No study population of its own. The review drew on previously reported clinical trials and on laboratory, animal and genetic research in malignant pleural mesothelioma. Table 1 lists ongoing trials taken from ClinicalTrials.gov.
• Exposure: Not an exposure study. Asbestos is mentioned only in the background, where the authors called the causal relationship between airborne asbestos and malignant pleural mesothelioma well established (citing earlier work). The review itself covers treatments.
• Main results:
  • Cited LUME-meso phase III trial (458 randomized patients with epithelioid histology): median progression-free survival was 6.8 months (95% CI 6.1–7.0) with nintedanib and 7.0 months (95% CI 6.7–7.2) with placebo, HR 1.01 (95% CI 0.79–1.30), p = 0.91
  • Cited PROMISE-meso phase III trial (second-line treatment): objective response rates were 22% with pembrolizumab vs. 6% with chemotherapy (p = 0.004). These responses did not translate into delayed progression or improved survival: median PFS was 2.5 vs. 3.4 months, HR 1.06 (95% CI 0.73–1.53), p = 0.76.
  • Cited MAPS2 phase 2 trial (relapsed patients): disease control at 12 weeks in 24 of 54 patients (44%) on nivolumab and 27 of 54 (50%) on nivolumab plus ipilimumab. Three (5%) treatment-related deaths were reported with the combination.
  • Cited MAPS phase 3 trial: adding bevacizumab to pemetrexed and cisplatin gave a median overall survival of 18.8 months vs. 16.1 months with pemetrexed plus cisplatin alone (HR 0.77, p = 0.0167)
  • Cited single-arm STELLAR trial of Tumor Treating Fields with chemotherapy: the 80 enrolled patients had a median overall survival of 18.2 months (95% CI 12.1-25.8). The authors said possible sampling bias in single-arm studies limits interpretation of these data.
  • Cited laboratory study: in human mesothelioma cell cultures, combining Tumor Treating Fields with cisplatin or pemetrexed led to a reduction in cell count
  • Cited animal study: combined with radiotherapy, the drug abemaciclib completely suppressed tumor growth in a mouse model of malignant pleural mesothelioma
• The authors' conclusion: The authors concluded that phase II results were often not replicated in larger randomized phase III trials. Because of cumulative toxicities and high costs, they said validated biomarkers are urgently needed to select patients for immunotherapy, and that well-designed, biomarker-driven trials are needed.
• Limitations the authors state:
  • The authors stated that evidence for checkpoint inhibitors in malignant pleural mesothelioma is still incomplete and rests mainly on non-randomized studies using surrogate end-points (a limitation of the evidence reviewed, not of the review itself).
  • The authors stated that evidence for intrapleural therapies is mainly from retrospective, small, single-institution studies, and that controlled randomized trials are required.
  • The authors noted potential sampling bias in single-arm studies, which they said limits interpretation of the STELLAR data.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Neoplasm, Mesothelioma, Immunotherapy, Clinical Trial.

Related studies

• Chemoimmunotherapy: an emerging strategy for the treatment of malignant mesothelioma — M.J. McCoy, A.K. Nowak, et al. (2009)
• Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies — L. Chiec, D.S. Bruno (2024)
• Emerging biological therapies for the treatment of malignant pleural mesothelioma — A.P. Davis, S.C. Kao, et al. (2021)
• Approved and emerging treatments of malignant pleural mesothelioma in elderly patients — G.L. Ceresoli, A. Rossi (2019)
• Emerging Strategies in the Diagnosis and Treatment of Pleural Mesothelioma: An Overview — R. Pagliaro, B. Leonardi, et al. (2026)
• MTAP Loss and Pleural Mesothelioma (PM): Current Treatment Strategies and Emerging Therapeutic Approaches — S. Cedres, L. Masfarre, et al. (2026)

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