The Role of Immunotherapy in the Treatment of Malignant Pleural Mesothelioma

Our plain-English summary of The Role of Immunotherapy in the Treatment of Malignant Pleural Mesothelioma, by S. Banerji, D.E. Meyers, C. Harlos, et al (Current Oncology, 2021).

The study

• Authors: S. Banerji, D.E. Meyers, C. Harlos, D.E. Dawe
• Journal: Current Oncology
• Published: 2021;28(6):4542-4551
• Type of article: Review
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward.

In plain English

This article is a review, not an original study. The authors summarized published trials of drug treatments for malignant pleural mesothelioma, a cancer whose incidence, they noted, is highly correlated with the local importation and use of asbestos. They covered chemotherapy trials first, then trials of immune therapies. In the CheckMate 743 trial, 605 patients were randomized for first-line treatment. Median overall survival was 14.1 months with platinum/pemetrexed chemotherapy and 18.1 months with nivolumab plus ipilimumab (HR 0.74, p = 0.002). In the CONFIRM trial of previously treated patients, median survival was 9.2 months with nivolumab and 6.6 months with placebo (HR 0.72, p 0.018). In the DETERMINE trial, survival was similar with tremelimumab and placebo (7.7 and 7.3 months). In the PROMISE-meso trial, pembrolizumab had a higher response rate than chemotherapy (22% versus 6%), but this did not translate into significant survival differences. The authors also described cell-based therapies that are still being tested. The authors concluded that immune checkpoint inhibitors now pose a viable alternative to chemotherapy in many patients. They added that the best timing and combinations are still being defined.

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: Published randomized and early-phase trials, plus ongoing Phase III trials, in patients with advanced malignant pleural mesothelioma. The article itself studied no patients.
• Exposure: Not an asbestos exposure study. The review covers treatments: cytotoxic chemotherapy, bevacizumab, immune checkpoint inhibitors (tremelimumab, pembrolizumab, nivolumab, ipilimumab, durvalumab) and cell-based therapies. Asbestos is mentioned only in the introduction, as linked to incidence.
• Main results:
  • Reviewed CheckMate 743 trial (first-line, 605 patients): median overall survival was 14.1 months in the platinum/pemetrexed control arm and 18.1 months in the nivolumab/ipilimumab arm (HR 0.74, p = 0.002).
  • In CheckMate 743, treatment-related Grade 3/4 serious events were more frequent in the nivolumab/ipilimumab arm (15% versus 6%).
  • Reviewed CONFIRM trial (332 previously treated patients): median overall survival was 9.2 months on nivolumab versus 6.6 months on placebo (HR 0.72, p 0.018).
  • Reviewed DETERMINE trial: median overall survival was similar, at 7.7 months with tremelimumab and 7.3 months with placebo (HR 0.92, p 0.41).
  • Reviewed PROMISE-meso trial (144 previously treated patients): the overall response rate was 22% with pembrolizumab and 6% with chemotherapy, without significant differences in progression-free or overall survival.
  • Reviewed earlier chemotherapy trial (Vogelzang, 2003): cisplatin/pemetrexed improved median overall survival from 9.3 to 12.1 months compared with cisplatin alone (HR 0.77, p = 0.02).
  • Reviewed MAPS trial: adding bevacizumab to cisplatin/pemetrexed improved median overall survival from 16.1 to 18.8 months (HR 0.77; p = 0.017) compared with placebo.
  • Reviewed combined analysis of 29 patients treated with dendritic cell therapy between 2006 and 2015: median overall survival was 27 months and 5-year overall survival was 20.7%.
• The authors' conclusion: The authors concluded that immune checkpoint inhibitors now pose a viable alternative to cytotoxic chemotherapy in many patients, either as first treatment or later. They added that the optimal timing and combinations of these therapies are still being defined.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Immunotherapy, Pleural Mesothelioma, Mesothelial Cells, Chemotherapy, Overall Survival, Bevacizumab, Ipilimumab (Yervoy), Nivolumab (Opdivo).

Related studies

• Multimodality treatment of malignant pleural mesothelioma with or without immunotherapy: does it change anything? — M. Lucchi, A. Picchi, et al. (2010)
• The next generation of immunotherapy: keeping lung cancer in check — A. Somasundaram, T.F. Burns (2017)
• Nivolumab Immunotherapy in Malignant Mesothelioma: A Case Report Highlighting a New Opportunity for Exceptional Outcomes — R.G. Jones, F. Karthik, et al. (2018)
• Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma — R. Govindan, C. Aggarwal, et al. (2022)
• What's the place of immunotherapy in malignant mesothelioma treatments? — M. Grégoire (2010)
• Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy — H. Wu, Y. Wang, et al. (2024)

Browse more research in Current Oncology, or return to medical research.