Analysis of new treatments proposed for malignant pleural mesothelioma raises concerns about the conduction of clinical trials in oncology

Our plain-English summary of Analysis of new treatments proposed for malignant pleural mesothelioma raises concerns about the conduction of clinical trials in oncology, by T. Meirson, V. Nardone, F. Pentimalli, et al (Journal of Translational Medicine, 2022).

The study

• Authors: T. Meirson, V. Nardone, F. Pentimalli, G. Markel, D. Bomze, M. D'Apolito, P. Correale, A. Giordano, L. Pirtoli, C. Porta, S.G. Gray, L. Mutti
• Journal: Journal of Translational Medicine
• Published: 2022;20(1):593
• Type of article: Letter
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In this commentary, using existing clinical trial data and FDA approvals we propose that there is currently a critical need for an appropriate balancing between the financial impact of new cancer drugs and their actual benefit for patients. By adopting "pleural mesothelioma" as our clinical model we summarize the most relevant pertinent and available literature on this topic, and use an analysis of the reliability of the trials submitted for registration and/or recently published as a case in point to raise concerns with respect to appropriate trial design, biomarker based stratification and to highlight the ongoing need for balancing the benefit/cost ratio for both patients and healthcare providers.

© 2022. The Author(s).

In plain English

This article was a commentary, not a new clinical study. The authors used published clinical trial data and FDA approvals to argue that the cost of new cancer drugs should be weighed against their actual benefit to patients. Their example was malignant pleural mesothelioma, which they described as an occupational cancer. They noted that six cancer drugs were approved by the FDA in 2019 to 2020 with no apparent control arm. The authors also reanalysed the three-year results of the CheckMate 743 trial of ipilimumab plus nivolumab. They reported uneven censoring of patients' data that favored the control arm (p = 0.026). After adjusting for this, the result was no longer statistically significant (hazard ratio 0.85, 95% confidence interval 0.71 to 1.02; p = 0.089). The trial's survival-inferred fragility index was 6 patients, 0.99% of the total sample. The authors said this means a small change in the study population could overturn the trial's conclusions. They said an apparent benefit limited to non-epithelioid mesothelioma should be treated as hypothesis generating. They concluded that new cancer treatments need more pre-clinical screening, greater statistical rigor in trials, and cost-effectiveness analysis.

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: Commentary that includes the authors' own statistical reanalysis of published trial data
• Who was studied: Published clinical trials and FDA approvals, chiefly the three-year results of the CheckMate 743 trial in malignant pleural mesothelioma, plus six drugs the FDA approved in 2019 to 2020
• Exposure: Not an asbestos exposure study. The treatments examined were the immune checkpoint inhibitors ipilimumab and nivolumab, plus other new drugs tested in mesothelioma. Mesothelioma is called an occupational cancer, but asbestos is not mentioned.
• Main results:
  • Six cancer drugs were approved by the FDA in 2019 to 2020 with no apparent control arm
  • In CheckMate 743, the authors found uneven censoring that favored the control arm (p = 0.026)
  • In CheckMate 743, after a sensitivity analysis accounting for the censoring imbalance, the result was no longer significant (HR 0.85, 95% CI 0.71 to 1.02; p = 0.089)
  • Using the three-year CheckMate 743 outcomes, the survival-inferred fragility index was 6 patients, 0.99% of the total sample size
  • In a virtual comparison, the overall survival curves of the MAPS trial and the updated CheckMate 743 trial overlapped for both intervention and control groups
• The authors' conclusion: The authors concluded that any new cancer treatment needs more pre-clinical screening, greater methodological rigor in trial statistics, and cost-effectiveness analysis. They said the non-epithelioid subgroup result from CheckMate 743 should be considered hypothesis generating.
• Limitations the authors state:
  • The authors said their virtual comparison of the MAPS and CheckMate 743 curves is less reliable than a head-to-head comparison in a randomized trial

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, Clinical Trial, Biomarker.

Related studies

• Systemic treatment of malignant pleural mesothelioma: new agents in clinical trials raise hope of relevant improvements — D.C. Christoph, W.E. Eberhardt (2014)
• Lung cancer patients' decisions about clinical trials and the theory of planned behavior — G.P. Quinn, C.L. Pratt, et al. (2011)
• A phase II trial of dovitinib in previously-treated advanced pleural mesothelioma: The Ontario Clinical Oncology Group — S.A. Laurie, D. Hao, et al. (2017)
• Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline Summary — H.L. Kindler, N. Ismaila, et al. (2018)
• Multicenter randomized controlled trial of the management of unresectable malignant mesothelioma proposed by the British Thoracic Society and the British Medical Research Council — D.J. Girling, M.F. Muers, et al. (2002)
• Phase II clinical trial of first or second-line treatment with bortezomib in patients with malignant pleural mesothelioma — D.A. Fennell, C. McDowell, et al. (2012)

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