Pleural Mesothelioma in the Era of Immunotherapy

Our plain-English summary of Pleural Mesothelioma in the Era of Immunotherapy, by M. Chevallier, F. Kim, A. Friedlaender, et al (Clinical Medicine Insights. Oncology, 2023).

The study

• Authors: M. Chevallier, F. Kim, A. Friedlaender, A. Addeo
• Journal: Clinical Medicine Insights. Oncology
• Published: 2023;17:11795549231178173
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Over the course of the last decade, immunotherapy has revolutionised the management of a great number of cancer types. The treatment of pleural mesothelioma, a rare and highly aggressive cancer, is also being transformed by immunotherapy. The recent combination of ipilimumab and nivolumab improved overall survival compared with platinum-based chemotherapy, irrespective of the histology, establishing immunotherapy as a front-line standard of care in advanced pleural mesothelioma. Yet, most patients do not derive long-term benefit from any of the available therapies, and we note a significant lack of predictive and prognostic biomarkers. After progressing on first-line therapy, patients have limited therapeutic options, and data are scarce about optimal sequencing. In this perspective, we discuss the current management of pleural mesothelioma, defining what we consider to be the therapeutic sequence based on performance status and tumour histology. We also highlight promising ongoing trials that could further shape the management of this rare disease.

© The Author(s) 2023.

In plain English

This article is a short review, which the authors call a perspective, about drug treatment for pleural mesothelioma that cannot be removed by surgery. It reported no new patient data. Instead it summarised published trials. The authors noted that this cancer mainly results from asbestos exposure. Among the trials described, the CheckMate 743 trial reported, after 3 years of follow-up, a median overall survival of 18.1 months with the immunotherapy drugs nivolumab plus ipilimumab, compared with 14.1 months with platinum-based chemotherapy. In that trial the benefit was statistically significant for non-epithelioid tumours (18.1 versus 8.8 months). For epithelioid tumours it showed only a trend that did not reach statistical significance (18.2 versus 16.7 months). Grade 3-4 adverse events occurred in 30.3% of patients in the immunotherapy group and 32% of patients in the chemotherapy group. The authors noted that no phase III trial data exist for treatment after first-line immunotherapy. They also noted that no biomarkers are currently available to guide the choice of treatment. The authors concluded that combined immunotherapy is a valid alternative to chemotherapy as first-line treatment.

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 (described by the authors as a brief perspective) summarising published clinical trials of treatments for pleural mesothelioma; no new patient data
• Who was studied: Not an original study population; the article reviewed trials in patients with unresectable (advanced) pleural mesothelioma
• Exposure: Asbestos exposure was not studied. The article states that pleural mesothelioma mainly results from asbestos exposure. It reviewed treatments: platinum-based chemotherapy (with or without bevacizumab) and immunotherapy (nivolumab, ipilimumab, pembrolizumab)
• Main results:
  • In a 2003 phase III trial cited by the review, cisplatin plus pemetrexed gave a longer median overall survival than cisplatin alone (12.1 months vs 9.3 months)
  • In the MAPS trial cited by the review, adding bevacizumab to first-line chemotherapy gave a significant overall survival benefit (18.8 months vs 16.1 months)
  • In the CheckMate 743 trial (3-year update), median overall survival was 18.1 months with nivolumab plus ipilimumab versus 14.1 months with chemotherapy (HR 0.73, 95% CI 0.61-0.87, P = 0.002)
  • In CheckMate 743, epithelioid tumours made up 75% of cases. In this group there was a trend for overall survival benefit that did not reach statistical significance (median 18.2 months vs 16.7 months, HR 0.85, 95% CI 0.69-1.04)
  • In CheckMate 743, non-epithelioid tumours had significantly longer median overall survival with immunotherapy (18.1 months vs 8.8 months, HR 0.48, 95% CI 0.34-0.69)
  • In CheckMate 743, grade 3-4 adverse events occurred in 30.3% of patients in the immunotherapy arm and 32% in the chemotherapy arm
  • The authors reported that after first-line immunotherapy there are no phase III study data on second-line treatment
  • The authors reported that no biomarkers are currently available to guide treatment choice. In CheckMate 743, tumour mutation burden was neither predictive nor prognostic
• The authors' conclusion: The authors concluded that, based on CheckMate 743, dual immunotherapy is a valid alternative to chemotherapy as front-line therapy for advanced pleural mesothelioma. They added that the best treatment after immunotherapy remains unclear
• Limitations the authors state:
  • The authors noted that in CheckMate 743, PD-L1 expression was not a stratification factor, so the apparent survival difference by PD-L1 level should be read with caution

Topics

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

Related studies

• 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)
• Depletion of Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy — F. Dammeijer, L.A. Lievense, et al. (2017)
• Chondroitin Sulfate Proteoglycan 4 and Its Potential As an Antibody Immunotherapy Target across Different Tumor Types — K.M. Ilieva, A. Cheung, et al. (2017)
• Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma — N.M. Mahaweni, M.E. Kaijen-Lambers, et al. (2013)

Browse more research in Clinical Medicine Insights. Oncology, or return to medical research.