Chemotherapy options versus "novel" therapies: how should we treat patients with malignant pleural mesothelioma

Our plain-English summary of Chemotherapy options versus "novel" therapies: how should we treat patients with malignant pleural mesothelioma, by M.J. Disselhorst, P. Baas (Translational Lung Cancer Research, 2020).

The study

• Authors: M.J. Disselhorst, P. Baas
• Journal: Translational Lung Cancer Research
• Published: 2020;9(Suppl 1):S77-S85
• Type of article: Review
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Today there are several options for the treatment of patients with malignant pleural mesothelioma (MPM). The therapeutic arsenal has expanded from only chemotherapy with or without surgery in selected cases to a variety of new compounds that target the malignant cell or its micro-environment. Immunotherapy has been the latest achievement and now single arm and randomized studies are being presented. A renewed interest has occurred in the combination of surgery, chemotherapy and radiation therapy. In this review we present the available data on previous and running studies and try to give a recommendation how to select the best patient for the most optimal therapy.

2020 Translational Lung Cancer Research. All rights reserved.

In plain English

This article was a review, not a new study. The authors described published trials and conference reports on treating malignant pleural mesothelioma. These covered chemotherapy, drugs that block blood-vessel growth, maintenance therapy, immunotherapy, therapies aimed at the protein mesothelin, arginine deprivation and surgery. They reported that a 2003 study by Vogelzang found cisplatin plus pemetrexed raised median overall survival from 10 to 13 months compared with cisplatin alone. In the French MAPS trial, adding bevacizumab gave a significant median survival benefit of 2.8 months. Single immune checkpoint drugs targeting PD-1 gave response rates of about 20%, mainly in phase II trials. In the PROMISE-meso trial, pembrolizumab produced more responses than chemotherapy (22% versus 6%) but did not improve progression-free or overall survival. The authors wrote that no reliable biomarkers have yet been found to select patients for the new therapies. The authors concluded that platinum with an antifolate drug, possibly with bevacizumab, remains the cornerstone of first-line treatment. They also wrote that patients should be encouraged to enroll in studies.

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 on treatment of malignant pleural mesothelioma
• Who was studied: Patients with malignant pleural mesothelioma (MPM) in previous and ongoing trials reviewed by authors from the Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam; no overall count or search method given
• Exposure: Not an asbestos exposure study; the review covered treatments: chemotherapy (cisplatin plus pemetrexed and others), angiogenesis inhibitors, maintenance therapies, epigenetic drugs, immune checkpoint inhibitors, dendritic cell immunotherapy, mesothelin-targeted therapy, arginine deprivation and surgery
• Main results:
  • Vogelzang study (2003, cited): cisplatin plus pemetrexed versus cisplatin alone raised median overall survival from 10 to 13 months
  • MAPS trial in France (cited): patients receiving bevacizumab added to standard care had a significant median overall survival benefit of 2.8 months
  • Phase 2 non-randomized studies of small molecules against VEGF receptors (cited): mostly no consistent activity, with response rates of 6-12%
  • Phase III thalidomide maintenance study (cited): median progression-free survival was 3.5 months in both groups, hazard ratio 0.99
  • Randomized phase II gemcitabine maintenance trial reported at ESMO 2019 (cited): median progression-free survival 6.2 months with gemcitabine versus 3.2 months with best supportive care; overall survival data awaited
  • Phase III vorinostat trial in second- and third-line treatment (cited): in 661 randomized patients, no difference in median progression-free or overall survival
  • Single-agent PD-1 checkpoint inhibitors (cited trials) had response rates of about 20%, mainly in phase II trials; the CTLA-4 inhibitor tremelimumab showed no benefit over placebo
  • PROMISE-meso phase III trial (cited): pembrolizumab versus chemotherapy (gemcitabine or vinorelbine) gave a significant difference in objective response rate (22% versus 6%) but no difference in progression-free or overall survival
  • Three phase II trials of checkpoint inhibitor combinations (cited) showed response rates between 25% and 38%
  • Randomized phase II trial of arginine deprivation with ADI-PEG20 (cited) in patients with ASS1-deficient mesothelioma: progression-free survival improved, overall survival did not
  • MARS randomized study in the UK of extra-pleural pneumonectomy (cited): considerable toxicity and morbidity and no signs of improvement
  • The authors stated that no reliable biomarkers had been found to select patients for any of the new therapies
• The authors' conclusion: The authors concluded that platinum with an antifolate, potentially including bevacizumab, remains the cornerstone of first-line treatment until a new randomized study beats it. In further lines no standard therapy exists, and checkpoint inhibitors may be preferred when available. Multimodality treatment is recommended only within clinical trials, and patients should be encouraged to enroll in studies.

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, Pleural Mesothelioma, Immunotherapy.

Related studies

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• Two-Stage Cytoreductive Surgery and Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma: Predictors of Overall Survival in an Intention-to-Treat Series — J.C. Leinwand, R.N. Taub, et al. (2020)
• Novel and Future Treatment Options in Mesothelioma: A Systematic Review — D. Štrbac, V. Dolžan (2022)
• Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743 — A. Scherpereel, P. Baas, et al. (2026)
• Hyperthermic intrathoracic chemotherapy (HITHOC) should be included in the guidelines for malignant pleural mesothelioma — M. Migliore, M. Ried, et al. (2021)
• Chemotherapy maintenance: an option for prolonged survival in malignant peritoneal mesothelioma? — S. Hofer, B. Sasse, et al. (2010)

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