What can independent research for mesothelioma achieve to treat this orphan disease?

Our plain-English summary of What can independent research for mesothelioma achieve to treat this orphan disease?, by A. Guazzelli, P. Meysami, E. Bakker, et al (Expert Opinion on Investigational Drugs, 2019).

The study

• Authors: A. Guazzelli, P. Meysami, E. Bakker, E. Bonanni, C. Demonacos, M. Krstic-Demonacos, L. Mutti
• Journal: Expert Opinion on Investigational Drugs
• Published: 2019;28(8):719-732
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival. Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy. Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment.

In plain English

This article is a review, not a new study. The authors examined clinical trials of treatments for malignant pleural mesothelioma (MPM) listed on clinicaltrials.gov, limited to trials funded by universities, the US National Institutes of Health (NIH) and charitable organisations. They also discussed laboratory and animal research. They covered chemotherapy, immunotherapy, targeted drugs, and 'repositioning' of drugs already approved for other illnesses. In the earlier trials they described, most new approaches showed limited benefit. For example, they reported that one trial found a median survival of 12.1 months with pemetrexed plus cisplatin versus 9.3 months with cisplatin alone, and that a phase III trial of thalidomide failed to improve survival. Several repositioned drugs, such as statins and aspirin, had not yet been tested in clinical trials in MPM. The authors attributed the failures to small numbers of patients, biases in trial design and the disease's particular biology. They concluded that investment in new ideas would be beneficial, particularly drug repositioning based on a solid scientific rationale, with good trial design and endpoints such as overall survival.

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: Review (narrative review with an expert opinion section) of preclinical and clinical research on mesothelioma treatment
• Who was studied: Clinical trials of treatments for malignant pleural mesothelioma listed on clinicaltrials.gov and funded by universities, the NIH and charitable organisations, plus published laboratory and animal studies. No search dates or total count of trials reviewed are given.
• Exposure: Not a study of asbestos exposure. The review covered treatments: chemotherapy combinations, immunotherapy, targeted (multitargeted) therapies, repositioned drugs and new small molecules.
• Main results:
  • The review reported that an earlier trial found a median survival of 12.1 months with pemetrexed plus cisplatin, compared with 9.3 months with cisplatin alone, in patients with advanced MPM.
  • The review described the MAPS trial as the most successful one: adding bevacizumab (Avastin) to cisplatin and pemetrexed significantly improved overall survival by two months compared with chemotherapy only.
  • The review reported that, in a phase II trial of single-agent erlotinib in 63 previously untreated MPM patients, there was no response among the 33 patients with measurable disease. Median overall survival was 10 months and progression-free survival was 2 months.
  • The review reported that, in a phase II trial of 125 patients given second- or third-line treatment, the twelve-week disease control rate was 42.6% with nivolumab and 51.9% with nivolumab plus ipilimumab.
  • The review reported that, in a randomised phase III study in MPM patients after first-line chemotherapy, thalidomide failed to improve overall survival: 10.6 months in the thalidomide group versus 12.9 months in the active supportive care group.
  • The review noted that several repositioned drugs had been studied only in laboratory or animal models and not yet in clinical trials in MPM. Examples are statins and aspirin.
  • The authors attributed the failure of current treatments to low numbers of MPM cases, bias in trial design, and the disease's unique biological features.
• The authors' conclusion: The authors concluded that investment in new ideas leading to new therapies for MPM would be beneficial. They pointed particularly to targeted drug repositioning based on a solid scientific rationale, with good clinical trial design and effective endpoints such as overall survival.

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: Mesothelioma, Pleural Mesothelioma, Neoplasm, Prognosis, Clinical Trial, Chemotherapy, Immunotherapy.

Related studies

• Promising investigational drug candidates in phase I and phase II clinical trials for mesothelioma — A. Guazzelli, E. Bakker, et al. (2017)
• Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy? — D. Signorelli, M. Macerelli, et al. (2016)
• Anti-CTLA-4 therapy for malignant mesothelioma — A. Guazzelli, E. Bakker, et al. (2017)
• Progression free survival rate at 9 and 18 weeks predict overall survival in patients with malignant pleural mesothelioma: an individual patient pooled analysis of 10 European Organisation for Research and Treatment of Cancer Lung Cancer Group studies and an independent study validation — B. Hasan, L. Greillier, et al. (2014)
• Tremelimumab for the treatment of malignant mesothelioma — A. Guazzelli, M. Hussain, et al. (2015)
• Network analysis of immunotherapy-induced regressing tumours identifies novel synergistic drug combinations — W.J. Lesterhuis, C. Rinaldi, et al. (2015)

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