Emerging therapies in malignant pleural mesothelioma

Our plain-English summary of Emerging therapies in malignant pleural mesothelioma, by M. Cinausero, K. Rihawi, F. Cortiula, et al (Critical Reviews in Oncology/hematology, 2019).

The study

• Authors: M. Cinausero, K. Rihawi, F. Cortiula, A. Follador, G. Fasola, A. Ardizzoni
• Journal: Critical Reviews in Oncology/hematology
• Published: 2019;144:102815
• Type of article: Review
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a rare cancer of the pleural surfaces frequently related to asbestos exposure. It is characterized by a poor prognosis even for patients treated with trimodality therapy, including surgery, chemotherapy and radiotherapy. Moreover, the majority of patients are not candidates for surgery due to disease advanced stage or medical comorbidities. For these patients, the survival rate is even lower and few therapeutic options are currently available. Nevertheless, many interesting novel approaches are under investigation, among which immunotherapy represents one of the most promising emerging strategies. In this review, we will discuss the role of new therapeutic options, particularly immunotherapy, and present the results of the most important and promising clinical trials.

Copyright © 2019 Elsevier B.V. All rights reserved.

In plain English

This article is a narrative review of treatments for malignant pleural mesothelioma, a rare cancer of the pleura that the authors describe as frequently related to asbestos exposure. The authors collected no new patient data. They summarized published and conference-reported studies of surgery, radiotherapy, chemotherapy and newer drugs, especially immunotherapy, and listed ongoing immunotherapy trials as of June 2019. Among the trials they described, a phase III trial reported median overall survival of 12.1 months with cisplatin plus pemetrexed versus 9.7 months with cisplatin alone. In a randomized phase II trial in previously treated patients, the objective response rate was 27.8% with nivolumab plus ipilimumab and 18.5% with nivolumab alone. The DETERMINE trial reported no survival benefit from tremelimumab compared with placebo. The authors concluded that immunotherapy is one of the most promising new strategies, with several trials ongoing or completed. They cautioned that findings suggesting PD-L1 is a useful marker come from small studies, and that validated biomarkers are lacking.

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 published and conference-reported clinical trials and preclinical studies of treatments for malignant pleural mesothelioma, with a table of ongoing immunotherapy trials
• Who was studied: Patients with malignant pleural mesothelioma (MPM) in the clinical trials reviewed. Ongoing immunotherapy trials were listed as of June 2019, excluding trials not yet recruiting.
• Exposure: Not an exposure study. The article reviewed treatments: surgery, radiotherapy, chemotherapy, antiangiogenic, anti-mesothelin, targeted and immunotherapy drugs. As background, and citing another source, it states that asbestos exposure is the most frequent cause of MPM, responsible for about 80% of diagnoses.
• Main results:
  • The review reports that the phase III EMPHACIS trial found median overall survival of 12.1 months with cisplatin plus pemetrexed, compared with 9.7 months in the control arm (single-agent cisplatin).
  • The review reports that the phase III MAPS trial found that adding bevacizumab to cisplatin-pemetrexed gave a benefit of about 2 months in both progression-free and overall survival, with increased toxicity.
  • The review reports that the phase III part of the LUME-Meso trial (nintedanib added to cisplatin-pemetrexed) did not meet its primary endpoint (progression-free survival) or its key secondary endpoints.
  • The review reports that a phase III trial of vorinostat versus placebo in 661 pretreated patients found a difference in overall survival (30.7 vs 27.1 weeks) that was not statistically significant.
  • The review reports that the phase Ib KEYNOTE-028 trial found a 40% clinical benefit rate with pembrolizumab in PD-L1 positive MPM patients.
  • The review reports preliminary results of a randomized phase II trial in pretreated MPM patients: objective response rate 27.8% with nivolumab plus ipilimumab versus 18.5% with nivolumab alone.
  • The review reports that the phase II DETERMINE trial found no survival benefit from tremelimumab compared with placebo in the intention-to-treat population (7.7 vs 7.3 months).
  • The review states that NCCN guidelines had incorporated pembrolizumab, and nivolumab with or without ipilimumab, as a treatment option for MPM patients after progression on first-line chemotherapy.
• The authors' conclusion: The authors concluded that immunotherapy is one of the most promising new therapeutic strategies for MPM, with several trials ongoing or already completed.
• Limitations the authors state:
  • The authors state that the subset findings suggesting PD-L1 expression is a useful biomarker should be interpreted cautiously because the studies were small.
  • The authors state that there are currently no validated biomarkers to identify which patients are more likely to benefit from immunotherapy or other treatments.
  • The authors note that patients in the multimodality (chemotherapy, surgery, radiotherapy) trials were highly selected.

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, Asbestos Exposure, Prognosis, Trimodality Therapy, Chemotherapy, Immunotherapy, Clinical Trial.

Related studies

• Emerging biological therapies for the treatment of malignant pleural mesothelioma — A.P. Davis, S.C. Kao, et al. (2021)
• Emerging translational therapies for mesothelioma — H.I. Pass, B.W. Robinson, et al. (1999)
• Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma — S.G. Gray (2021)
• Approved and emerging treatments of malignant pleural mesothelioma in elderly patients — G.L. Ceresoli, A. Rossi (2019)
• Malignant pleural mesothelioma: update on treatment options with a focus on novel therapies — A.R. Haas, D.H. Sterman (2013)
• Effects of combined therapies on the survival of pleural mesothelioma patients treated in Brescia, 1982-2006 — P.G. Barbieri, A. Marinaccio, et al. (2012)

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