Progress in the Management of Malignant Pleural Mesothelioma in 2017

Our plain-English summary of Progress in the Management of Malignant Pleural Mesothelioma in 2017, by A.J. McCambridge, A. Napolitano, A.S. Mansfield, et al (Journal of Thoracic Oncology, 2018).

The study

• Authors: A.J. McCambridge, A. Napolitano, A.S. Mansfield, D.A. Fennell, Y. Sekido, A.K. Nowak, T. Reungwetwattana, W. Mao, H.I. Pass, M. Carbone, H. Yang, T. Peikert
• Journal: Journal of Thoracic Oncology
• Published: 2018;13(5):606-623
• Type of article: Review
• Cited by: 60 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an uncommon, almost universally fatal, asbestos-induced malignancy. New and effective strategies for diagnosis, prognostication, and treatment are urgently needed. Herein we review the advances in MPM achieved in 2017. Whereas recent epidemiological data demonstrated that the incidence of MPM-related death continued to increase in United States between 2009 and 2015, new insight into the molecular pathogenesis and the immunological tumor microenvironment of MPM, for example, regarding the role of BRCA1 associated protein 1 and the expression programmed death receptor ligand 1, are highlighting new potential therapeutic strategies. Furthermore, there continues to be an ever-expanding number of clinical studies investigating systemic therapies for MPM. These trials are primarily focused on immunotherapy using immune checkpoint inhibitors alone or in combination with other immunotherapies and nonimmunotherapies. In addition, other promising targeted therapies, including pegylated adenosine deiminase (ADI-PEG20), which focuses on argininosuccinate synthase 1-deficient tumors, and tazemetostat, an enhancer of zeste 2 polycomb repressive complex 2 subunit inhibitor of BRCA1 associated protein 1 gene (BAP1)-deficient tumors, are currently being explored.

Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This article was a review, not an original study. The authors searched MEDLINE for 2017 publications on malignant pleural mesothelioma. They selected those they judged relevant to epidemiology, pathology, genetics, diagnosis, staging and treatment, and added clinical-trial abstracts from three 2017 cancer meetings. It summarized previously published research, some of it coauthored by the review's own authors, rather than presenting new data. A US Centers for Disease Control report counted 45,221 mesothelioma-related deaths in the United States between 1999 and 2015. A study of 12 lung tissue samples suggested that chrysotile asbestos fibers also stay in the lung a long time. In a trial of 87 evaluable patients, adding nintedanib to chemotherapy lengthened progression-free survival by 3.7 months compared with placebo, but the overall survival difference was not statistically significant. The DETERMINE trial, comparing tremelimumab with placebo in previously treated unresectable mesothelioma, failed to demonstrate differences in overall or progression-free survival. A database study of 271 patients who had extrapleural pneumonectomy and 1036 who had pleurectomy/decortication found no statistically significant difference in overall survival. The authors concluded that pemetrexed-based chemotherapy, with or without bevacizumab, remained the standard of care for most patients.

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 publications from 2017, with the authors selecting studies by expert opinion. Some of the cited studies were coauthored by the review's own authors.
• Who was studied: Publications on malignant pleural mesothelioma from 2017 identified through MEDLINE, plus abstracts of ongoing or recently completed clinical trials presented at the 2017 ASCO, 2017 ESMO and 2017 World Congress of Lung Cancer meetings
• Exposure: Not an exposure study. The review covers diagnosis and treatment of malignant pleural mesothelioma. Its epidemiology section summarizes 2017 studies on asbestos, including one on how long chrysotile fibers persist in human lungs.
• Main results:
  • From a CDC report cited by the review: 45,221 mesothelioma-related deaths in the United States between 1999 and 2015, with a 4.8% increase in deaths over that period
  • From a reviewed study across 230 countries: the global burden of mesothelioma deaths was extrapolated to about 38,400 per year
  • From reviewed 2017 studies: loss of BAP1 was found in more than 60% of both pleural and peritoneal mesotheliomas
  • LUME-Meso phase II trial: among 87 evaluable patients (44 nintedanib, 43 placebo), nintedanib added to chemotherapy improved progression-free survival by 3.7 months compared with placebo (p=0.01)
  • LUME-Meso: median overall survival was 18.3 months in the nintedanib group versus 14.2 months, a difference that was not statistically significant
  • DETERMINE trial: comparing tremelimumab with placebo in previously treated unresectable mesothelioma, it failed to demonstrate differences in overall or progression-free survival
  • KEYNOTE-028 trial: of 25 patients with PD-L1-positive mesothelioma given pembrolizumab, 20% had a partial response and 52% had stable disease
  • ADI-PEG20 trial (44 patients given ADI-PEG20 plus best supportive care, 24 given best supportive care only): median progression-free survival was 3.2 months in the treatment group versus 2.0 months in the control group (p =0.03)
  • Phase II trial in 248 patients with mesothelin-positive mesothelioma: anetumab ravtansine compared with vinorelbine did not show a difference between the treatment groups
  • National Cancer Database study of 271 patients who had extrapleural pneumonectomy (EPP) and 1036 who had pleurectomy/decortication (P/D): no statistically significant difference in overall survival (19 months EPP, 16 months P/D; p=0.120)
• The authors' conclusion: The authors concluded that pemetrexed-based chemotherapy, with or without bevacizumab, remained the standard of care for most patients

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Tumor Microenvironment, Immunotherapy, checkpoint inhibitors, Pegargiminase (ADI-PEG20), BAP1.

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