Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future

Our plain-English summary of Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future, by F. Nicolini, M. Bocchini, G. Bronte, et al (Frontiers in Oncology, 2019).

The study

• Authors: F. Nicolini, M. Bocchini, G. Bronte, A. Delmonte, M. Guidoboni, L. Crinò, M. Mazza
• Journal: Frontiers in Oncology
• Published: 2019;9:1519
• Type of article: Review
• Cited by: 71 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8-14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing. The exact molecular mechanisms that explain the carcinogenicity of asbestos are not known. Standard therapeutic strategies for MPM include surgery, often coupled with chemotherapy and/or radiotherapy, in a small percentage of eligible patients and chemotherapy in tumors considered unresectable with or without adjuvant radiotherapy. In recent years, several new therapeutic avenues are being explored. These include angiogenesis inhibitors, synthetic lethal treatment, miRNA replacement, oncoviral therapies, and the fast-growing field of immunotherapy alone or in combination with chemotherapy. Of particular promise are the multiple options offered by immunotherapy: immune checkpoint inhibitors, tumor vaccines, and therapies taking advantage of tumor-specific antigens, such as specific therapeutic antibodies or advanced cell-based therapies exemplified by the CAR-T cells. This review comprehensively presents both old and new therapeutic options in MPM, focusing on the results of the numerous recent and on-going clinical trials in the field, including the latest data presented at international meetings (AACR, ASCO, and ESMO) this year, and concludes that more work has to be done in the framework of tailored therapies to identify reliable targets and novel biomarkers to impact MPM management.

Copyright © 2020 Nicolini, Bocchini, Bronte, Delmonte, Guidoboni, Crinò and Mazza.

In plain English

This article is a mini review, not a new study. The authors, from a cancer institute in Meldola, Italy, summarized published and ongoing clinical trials of treatments for malignant pleural mesothelioma, a cancer of the pleural surface they describe as associated with asbestos exposure. They covered standard care: surgery, radiotherapy and chemotherapy, with cisplatin-pemetrexed described as the only FDA- and EMA-approved frontline therapy. They also covered newer approaches, including blood-vessel growth inhibitors, synthetic lethal treatments, immune checkpoint inhibitors, miRNA replacement, tumor treating fields, virus-based therapies, dendritic cell vaccines, and therapies aimed at mesothelin and other targets, such as CAR-T cells. In trials they reported, the phase III MAPS study found that adding bevacizumab to cisplatin-pemetrexed raised median overall survival from 16.1 to 18.8 months. The phase III LUME-Meso trial of nintedanib missed its primary progression-free survival endpoint. In the phase III PROMISE-meso trial, pembrolizumab did not improve median overall or progression-free survival compared with chemotherapy. The authors concluded that clinical practice had not changed in decades and that chemotherapy remained the only standard option. They added that newer therapies with good early results needed confirmation in larger trials.

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: Mini review of published and ongoing clinical trials of treatments for malignant pleural mesothelioma (no new patient data)
• Who was studied: No study population of its own; the review covers clinical trials in malignant pleural mesothelioma patients, including recent and ongoing trials and data presented at international meetings (AACR, ASCO, ESMO)
• Exposure: Not an exposure study. The review is about treatments; asbestos is mentioned only as the exposure associated with malignant pleural mesothelioma. No fiber types or doses are discussed.
• Main results:
  • The authors reported that cisplatin-pemetrexed was the only FDA- and EMA-approved frontline therapy for malignant pleural mesothelioma.
  • In the phase III MAPS study (as reported by the review), adding bevacizumab to cisplatin-pemetrexed chemotherapy increased median overall survival from 16.1 to 18.8 months and progression-free survival from 7.3 to 9.2 months.
  • In the phase III LUME-Meso trial of nintedanib plus chemotherapy (as reported by the review), the primary progression-free survival endpoint failed, not confirming earlier phase II results.
  • In the phase II COMMAND trial (as reported by the review), maintenance defactinib after frontline chemotherapy did not improve progression-free or overall survival compared with placebo.
  • In the DETERMINE trial (as reported by the review), tremelimumab as second- or third-line treatment showed no benefit over placebo.
  • In two phase II studies of nivolumab as second- or third-line treatment, NivoMes and MERIT (as reported by the review), objective response rates were 24.0% and 29.4%, respectively.
  • In the phase III PROMISE-meso trial in relapsed patients (as reported by the review), pembrolizumab did not improve median overall or progression-free survival compared with single-agent chemotherapy, although the objective response rate was higher for pembrolizumab (22% vs. 6%).
  • In the phase II MAPS2 trial in relapsed patients (as reported by the review), the primary endpoint of disease control at 12 weeks was reached by ipilimumab plus nivolumab (50%) but not by nivolumab alone (44%). Severe treatment-related side effects occurred in 17% of patients.
  • In the phase II STELLAR trial (as reported by the review), patients treated with tumor treating fields plus chemotherapy had a median overall survival of 18.2 months and low systemic toxicity.
  • Preliminary meeting results for mesothelin-targeted CAR-T cells (as reported by the review) showed an objective response rate of 36.8% and a disease control rate of 57.8% in a cohort treated off protocol in combination with pembrolizumab.
• The authors' conclusion: The authors concluded that clinical practice had not changed over the past decades and chemotherapy remained the only standard option. In their view, anti-angiogenic therapies and immune checkpoint inhibitors given alone have had little impact on survival, and checkpoint inhibitor combinations come with relevant toxicities. They placed hope in innovative therapies that showed good preliminary efficacy, but said these results need confirmation in larger trials.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Median Overall Survival, Biomarker, Chemotherapy, Unresectable, Angiogenesis, Immunotherapy.

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