Immunotherapy for mesothelioma: a critical review of current clinical trials and future perspectives

Our plain-English summary of Immunotherapy for mesothelioma: a critical review of current clinical trials and future perspectives, by S.G. Gray, L. Mutti (Translational Lung Cancer Research, 2020).

The study

• Authors: S.G. Gray, L. Mutti
• Journal: Translational Lung Cancer Research
• Published: 2020;9(Suppl 1):S100-S119
• Type of article: Review
• Cited by: 54 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

At the clinical level the role of immunotherapy in cancer is currently at a pivotal point. Therapies such as checkpoint inhibitors are being approved at many levels in cancers such as non-small cell lung cancer (NSCLC). Mesothelioma is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Various clinical trials for checkpoint inhibitors have been conducted in this rare disease, and suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer. Most recently approved as a salvage therapy in mesothelioma was granted in Japan, regulatory approval for their use in the clinic elsewhere lags. In this article we review the current pertinent clinical trials of immunotherapies in malignant mesothelioma, discuss the current issues that may affect the clinical outcomes of such therapies and further evaluate potential candidate new avenues that may become future targets for immunotherapy in this cancer.

2020 Translational Lung Cancer Research. All rights reserved.

In plain English

This article is a review, not a new study of patients. The authors reviewed clinical trials of immunotherapy for malignant mesothelioma, which the article describes as associated with prior asbestos exposure. They covered checkpoint inhibitor drugs given before surgery, as first treatment, and after earlier treatment had failed, as well as oncolytic viruses, CAR-T cells and dendritic cell vaccines. In the trials described, DETERMINE (571 patients) found no difference in median overall survival: 7.7 months with tremelimumab versus 7.3 months with placebo. In MAPS-2, median overall survival was 11.9 months with nivolumab alone and 15.9 months with nivolumab plus ipilimumab. Japan approved nivolumab in 2018 for mesothelioma after earlier treatment. In the authors' own analysis of a public mesothelioma gene dataset, high B7H3 expression was associated with worse overall survival (hazard ratio 1.95, 95% confidence interval 1.44 to 2.66). The authors noted that many trials were small and lacked comparison groups. They concluded that the results support further development of checkpoint inhibitors, and that phase II/III results are awaited.

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 clinical trials of immunotherapy in mesothelioma, with a small analysis by the authors of a public gene-expression dataset (TCGA mesothelioma)
• Who was studied: Patients with malignant mesothelioma (mainly malignant pleural mesothelioma) enrolled in the clinical trials reviewed; for the authors' own analysis, the TCGA mesothelioma dataset
• Exposure: Not a study of asbestos exposure. The 'exposures' reviewed were treatments: checkpoint inhibitors (tremelimumab, pembrolizumab, nivolumab, ipilimumab, durvalumab, atezolizumab, avelumab), oncolytic viruses, CAR-T cells and dendritic cell vaccines. Asbestos is mentioned only as the exposure associated with mesothelioma.
• Main results:
  • Reported from the DETERMINE trial (571 patients whose disease had progressed after previous treatment): median overall survival did not differ, at 7.7 months with tremelimumab versus 7.3 months with placebo
  • Reported from interim PROMISE-meso results: median progression-free survival was 2.5 months in 73 patients given pembrolizumab and 3.4 months in 71 patients given gemcitabine or vinorelbine chemotherapy, not significantly different
  • Reported from the MAPS-2 trial (125 patients): median overall survival was 11.9 months with nivolumab alone and 15.9 months with nivolumab plus ipilimumab
  • In 2018, Japan's Ministry of Health, Labor and Welfare approved nivolumab as a salvage therapy in mesothelioma, based on the MERIT trial
  • Authors' own analysis of the TCGA mesothelioma dataset: high B7H3 (CD276) expression was associated with worse overall survival, hazard ratio 1.95 (95% CI 1.44 to 2.66)
  • Authors' own analysis of the TCGA mesothelioma dataset: high OX40L expression was associated with worse overall survival, hazard ratio 1.32 (1.15 to 1.51); no significant survival difference was seen for OX40
• The authors' conclusion: The authors concluded that the trial results continue to support further development of checkpoint inhibitors, alone or in combination, in mesothelioma. They also said that results of ongoing phase II/III trials are awaited.
• Limitations the authors state:
  • The authors noted that many of the smaller trials reviewed were early-phase trials with few patients, which limits how robust the data are and the scope for subgroup analyses
  • The authors noted that several trials had a single-arm, non-randomized design, which prevents direct comparison with other treatments

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Mesothelioma, Clinical Trial, checkpoint inhibitors, Non-Small Cell Lung Cancer, Prognosis.

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