Malignant pleural mesothelioma: new hope in the horizon with novel therapeutic strategies

Our plain-English summary of Malignant pleural mesothelioma: new hope in the horizon with novel therapeutic strategies, by J. Remon, N. Reguart, J. Corral, et al (Cancer Treatment Reviews, 2015).

The study

• Authors: J. Remon, N. Reguart, J. Corral, P. Lianes
• Journal: Cancer Treatment Reviews
• Published: 2015;41(1):27-34
• Type of article: Review
• Cited by: 59 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy of the pleura, with a strong causal link to asbestos exposure. MPM incidence has been increasing in recent years and it is not expected to fall off in the next two decades. Prognosis of MPM patients is modest since the vast majority of patients are diagnosed at advanced stage and because platinum-based chemotherapy remains the cornerstone of treatment, with no standard second line treatment. Most current efforts to improve outcomes are based on a better understanding of the stromal compartment and deregulated pathways leading ultimately to the design of clinical trials based on novel therapeutic approaches such as immunotherapy or molecular-directed compounds. This review seeks to update the last clinical trials investigating novel agents in unresectable MPM.

Copyright © 2014 Elsevier Ltd. All rights reserved.

In plain English

This article was a review, not an original study. The authors summarized published and ongoing clinical trials of drug treatments for malignant pleural mesothelioma (cancer of the lining around the lungs) that cannot be removed by surgery. They described the disease as having a strong causal link to asbestos exposure. The review stated that cisplatin combined with an antifolate drug was the standard first treatment. In two earlier phase III trials this combination added about 3 months of median survival over cisplatin alone (12.1 vs. 9.3 months with pemetrexed). The review also stated that there was no standard second-line treatment. Results it reported for newer drugs were mixed. Vorinostat did not improve overall survival in a trial of 660 previously treated patients. Thalidomide maintenance in a trial of 222 patients showed no benefit in progression-free or overall survival. The arginine-lowering drug ADI-PEG20 lengthened time without progression in patients with ASS1-deficient tumors. In a 29-patient trial of tremelimumab, an immunotherapy drug, 2 patients had a tumor response. The authors concluded that trial success depends on selecting patients by biomarkers and that immunotherapy warrants further evaluation.

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 ongoing clinical trials
• Who was studied: No original patient population. The review covered clinical trials of novel agents in patients with unresectable or advanced malignant pleural mesothelioma (MPM).
• Exposure: Not an exposure study; the article is about treatment. It describes mesothelioma as strongly causally linked to asbestos exposure and does not study fiber types.
• Main results:
  • The review reported that in two earlier phase III trials, cisplatin plus an antifolate (pemetrexed or raltitrexed) gave about 3 months of median overall survival benefit over cisplatin alone. The figures were 12.1 vs. 9.3 months in the pemetrexed trial and 11.4 vs. 8.8 months in the raltitrexed trial.
  • The review stated that MPM had no standard second-line treatment and no widely approved salvage therapy beyond antifolate treatment. It also discussed options such as pemetrexed retreatment in fit patients and vinorelbine as a palliative option.
  • The review reported that the phase III VANTAGE 014 trial compared vorinostat with best supportive care in 660 pre-treated advanced MPM patients. There was no improvement in overall survival (30.7 vs. 27.1 weeks, p = 0.858).
  • The review reported that thalidomide maintenance in the randomized phase III NVALT 5 trial (222 randomized patients, after pemetrexed-cisplatin induction) did not show any benefit in progression-free survival or overall survival. The review's text calls the comparison group placebo, while the cited trial's title describes an open-label comparison with supportive care.
  • The review reported that in the phase II ADAM trial in patients with ASS1-deficient MPM, ADI-PEG20 plus best supportive care gave longer progression-free survival than best supportive care alone (98 vs. 59 days, HR 0.53, p = 0.02).
  • The review reported on a single-arm phase II trial of tremelimumab in 29 chemo-resistant advanced mesothelioma patients. Of the 29, 2 had an objective response. The 1-year survival rate was 48.3% and the 2-year rate was 36.7%.
• The authors' conclusion: The authors concluded that the success of phase II and III trials in MPM depends on selecting patients by biomarkers. They said smaller randomized phase II trials should replace large randomized trials. They also said immunotherapy, especially anti-CTLA4 agents, warrants further evaluation.

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, Pleura, Asbestos Exposure, Prognosis, Chemotherapy, Clinical Trial, Immunotherapy, Unresectable.

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• New horizons from novel therapies in malignant pleural mesothelioma — M. Sayan, S. Mamidanna, et al. (2020)
• New therapeutic strategies for malignant pleural mesothelioma — M.A. Bonelli, C. Fumarola, et al. (2017)

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