Immunotherapy in Malignant Pleural Mesothelioma

Our plain-English summary of Immunotherapy in Malignant Pleural Mesothelioma, by C.J. de Gooijer, F.J. Borm, A. Scherpereel, et al (Frontiers in Oncology, 2020).

The study

• Authors: C.J. de Gooijer, F.J. Borm, A. Scherpereel, P. Baas
• Journal: Frontiers in Oncology
• Published: 2020;10:187
• Type of article: Review
• Cited by: 61 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The only registered systemic treatment for malignant pleural mesothelioma (MPM) is platinum based chemotherapy combined with pemetrexed, with or without bevacizumab. Immunotherapy did seem active in small phase II trials. In this review, we will highlight the most important immunotherapy-based research performed and put a focus on the future of MPM. PD-(L)1 inhibitors show response rates between 10 and 29% in phase II trials, with a wide range in progression free (PFS) and overall survival (OS). However, single agent pembrolizumab was not superior to chemotherapy (gemcitabine or vinorelbine) in the recent published PROMISE-Meso trial in pre-treated patients. In small studies with CTLA-4 inhibitors there is evidence for response in some patients, but it fails to show a better PFS and OS compared to best supportive care in a randomized study. A combination of PD-(L)1 inhibitor with CTLA-4 inhibitor seem to have a similar response as PD-(L)1 monotherapy. The first results of combining durvalumab (PD-L1 blocking) with cisplatin-pemetrexed in the first line are promising. Another immune treatment is Dendritic Cell (DC) immunotherapy, which is recently tested in mesothelioma, shows remarkable anti-tumor activity in three clinical studies. The value of single agent checkpoint inhibitors is limited in MPM. There is an urgent need for biomarkers to select the optimal candidates for immunotherapy among MPM patients in terms of efficacy and tolerance. Results of combination checkpoint inhibitors with chemotherapy are awaiting.

Copyright © 2020 de Gooijer, Borm, Scherpereel and Baas.

In plain English

This article was a mini review. The authors searched the literature and summarized trials of immunotherapy drugs for malignant pleural mesothelioma. It does not discuss asbestos exposure. In the PROMISE-meso trial of previously treated patients, pembrolizumab was not superior to chemotherapy in progression-free survival (median 2.5 versus 3.4 months). In DETERMINE, 571 patients were randomized to tremelimumab or placebo, with no significant differences in response or survival. In MAPS2, nivolumab with or without ipilimumab showed clinical activity. In the single-arm DREAM trial, 54 first-line patients given durvalumab with cisplatin-pemetrexed had a 48% response rate by mRECIST but median progression-free survival of only 6.9 months, which the authors said should be placed in perspective against standard chemotherapy. In one dendritic cell study, three of nine patients had a partial response; two had recently received chemotherapy, which the authors said might affect the result. The authors noted results varied widely, possibly reflecting small study sizes and differing response criteria. They concluded that immunotherapy seems to bring hope for selected patients, that crucial questions remain, and that biomarkers are urgently needed.

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: Mini review of published and conference-reported immunotherapy trials
• Who was studied: No new patients were studied. The review covered trials in patients with malignant pleural mesothelioma (MPM), identified through a literature search.
• Exposure: Not addressed. The review concerns immunotherapy treatments (PD-1/PD-L1 and CTLA-4 inhibitors, combinations with chemotherapy, dendritic cell therapy), not asbestos exposure.
• Main results:
  • PROMISE-meso trial (pembrolizumab vs chemotherapy, previously treated patients): the primary endpoint was not met. Median progression-free survival was 2.5 months (95% CI 2.1–4.2) for pembrolizumab vs 3.4 months (2.2–4.3) for chemotherapy, HR 1.06 [0.73–1.53], p = 0.76.
  • PROMISE-meso trial: response rate was 22% in the pembrolizumab arm vs 6% in the chemotherapy arm (p = 0.004).
  • Three single-agent nivolumab studies reported objective response rates between 15 and 29% and disease control rates between 44 and 68%.
  • DETERMINE trial: 571 patients randomized 2:1 to tremelimumab or placebo, with no significant differences in response or survival.
  • MAPS2 trial, nivolumab alone vs nivolumab plus ipilimumab: disease control rate 40% vs 52%, objective response rate 19% vs 28%, median progression-free survival 4.0 vs 5.6 months.
  • DREAM trial, a single-arm phase II study: in 54 first-line patients given durvalumab with cisplatin-pemetrexed, objective response rate was 48% by mRECIST and median progression-free survival was 6.9 months.
  • The authors said the DREAM results should be placed in perspective, after noting that standard platinum-pemetrexed chemotherapy has response rates around 45% and median progression-free survival of up to 7.3 months.
  • First dendritic cell study (2010): 3 of 9 MPM patients had a partial response in the first 8 weeks. Two of these patients had received chemotherapy shortly before dendritic cell treatment, which the authors said might have affected the result.
• The authors' conclusion: The authors concluded that immunotherapy seems to bring hope for a selected group of MPM patients but that crucial questions remain unanswered, and that biomarkers are urgently needed to select patients.
• Limitations the authors state:
  • The authors noted that the reviewed studies varied widely in outcome, possibly because most were small and differed in pathology and study execution.
  • The authors noted that the reviewed studies used different RECIST response criteria, which may explain the wide range of reported response rates.
  • The authors noted that disease control rate was measured at different time points across studies, making comparison hard.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Pleural Mesothelioma, Chemotherapy, Pemetrexed (Alimta), Bevacizumab, Overall Survival, Pembrolizumab (Keytruda), Gemcitabine.

Related studies

• Role of Immunotherapy in Small Cell Lung Cancer, Thymic Epithelial Tumors, and Mesothelioma — C.L. Hann, A. Scherpereel, et al. (2019)
• Dynamics and survival associations of T cell receptor clusters in patients with pleural mesothelioma treated with immunotherapy — A.P. Desai, F. Kosari, et al. (2023)
• Immunotherapy in relapsed mesothelioma — S. Brosseau, X. Dhalluin, et al. (2018)
• Mesothelin Immunotherapy for Cancer: Ready for Prime Time? — R. Hassan, A. Thomas, et al. (2016)
• COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function — J.D. Veltman, M.E. Lambers, et al. (2010)
• Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis — T. Berghmans, M. Paesmans, et al. (2002)

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