Current Management and Future Perspective in Pleural Mesothelioma

Our plain-English summary of Current Management and Future Perspective in Pleural Mesothelioma, by R. Shah, L.V. Klotz, J. Glade (Cancers, 2022).

The study

• Authors: R. Shah, L.V. Klotz, J. Glade
• Journal: Cancers
• Published: 2022;14(4)
• Type of article: Review
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma is an aggressive malignancy arising from pleural mesothelial cell lining, predominantly associated with prior exposure to asbestos. The ban on asbestos use has led to its lower incidence in many countries, but globally the disease burden is expected to rise. Therefore, well-planned research is needed to develop more effective, tolerable and affordable drugs. The development of novel treatment has been too slow, with only two regimens of systemic therapy with robust phase 3 data approved formally to date. The treatment scenario for resectable disease remains controversial. However, recent developments in the understanding of disease and clinical trials have been encouraging, and may add better treatment options in the coming years. In this review, we discuss the current treatment options for pleural mesothelioma and shed light on some recent studies and ongoing trials.

In plain English

This article was a review of current treatment and ongoing research for pleural mesothelioma. It did not study patients itself. It described the published results of other trials. As background, it stated that in 70–80% of cases there is a known history of asbestos exposure. It also noted that a germline BAP1 mutation seems to lower the cumulative asbestos exposure needed to develop the disease. Among the trials it described, CheckMate-743, in 605 previously untreated patients, reported overall survival of 18.1 months with nivolumab plus ipilimumab versus 14.1 months with cisplatin or carboplatin plus pemetrexed (HR 0.74). The largest difference was in non-epithelioid tumors. In patients whose disease had progressed after earlier treatment, the CONFIRM trial reported overall survival of 9.2 months with nivolumab versus 6.6 months with placebo. The authors described the role of radical surgery as still controversial. They concluded that nivolumab plus ipilimumab outperforms platin and pemetrexed chemotherapy, but that chemotherapy remains a robust option, especially for the epithelioid subtype. They also concluded that carefully selected patients with resectable disease should be treated in high-volume centers, preferably within a clinical trial.

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 treatment options, recent studies and ongoing trials in pleural mesothelioma (not original research)
• Who was studied: No patients were studied directly. The review covered published studies and ongoing clinical trials in malignant pleural mesothelioma. The number of studies reviewed is not stated.
• Exposure: Not an exposure study. Asbestos is mentioned only as background: the review states that 70–80% of cases have a known history of asbestos exposure. The review's subject is treatments: chemotherapy, immune checkpoint inhibitors, surgery, radiotherapy and targeted therapies.
• Main results:
  • The review described another study (Betti et al.) suggesting that people with a germline BAP1 mutation seem to need lower cumulative asbestos exposure to develop pleural mesothelioma.
  • As reported in the review, the CheckMate-743 trial in 605 treatment-naive patients found overall survival of 18.1 months with nivolumab plus ipilimumab versus 14.1 months with cisplatin or carboplatin plus pemetrexed (HR 0.74).
  • In CheckMate-743, as reported in the review, the survival difference was largest in the non-epithelioid subtype: 8.8 months with chemotherapy vs 18.1 months with immunotherapy (HR 0.46). In the epithelioid subtype it was 16.5 vs 18.7 months (HR 0.86).
  • In the 3-year CheckMate-743 update, as reported in the review, 23% of the nivolumab plus ipilimumab group were alive at 3 years vs 15% of the chemotherapy group. Grade 3 or 4 adverse events occurred in 15% vs 6%, respectively.
  • As reported in the review, cisplatin plus pemetrexed (with vitamin B12 and folic acid) improved overall survival compared with cisplatin alone: 12.1 vs 9.3 months (HR 0.76).
  • As reported in the review, the CONFIRM trial randomized 332 previously treated patients 2:1 to nivolumab or placebo. Overall survival was 9.2 months with nivolumab vs 6.6 months with placebo (HR 0.72; p = 0.018).
  • As reported in the review, the DETERMINE trial randomized 571 previously treated patients to tremelimumab or placebo. It found no difference in overall survival: 7.7 vs 7.3 months (HR 0.92, p = 0.41).
  • The review described the role of radical surgery within multimodal treatment as remaining controversial.
• The authors' conclusion: The authors concluded that nivolumab plus ipilimumab outperforms platin and pemetrexed in both overall survival and quality of life. They added that platin and pemetrexed remains a robust option, especially for the epithelioid subtype.
• Limitations the authors state:
  • The authors stated limitations of the evidence base they reviewed, rather than of the review itself: low incidence, individual heterogeneity of the disease, a lack of well-designed randomized trials, and non-standardized treatment approaches.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelial Cells, Systemic Therapy, Clinical Trial.

Related studies

• Immunotherapy for mesothelioma: a critical review of current clinical trials and future perspectives — S.G. Gray, L. Mutti (2020)
• Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors-Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment — Y. Yoshikawa, K. Kuribayashi, et al. (2020)
• Stem Cells Application in Thoracic Surgery: Current Perspective and Future Directions — F. Petrella, L. Spaggiari (2018)
• Current and Future Management of Malignant Mesothelioma: A Consensus Report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation — A.S. Tsao, O.W. Lindwasser, et al. (2018)
• Chemotherapy for malignant pleural mesothelioma: a review of current management and a look to the future — A.K. Nowak (2012)
• Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma — H.R. Alexander, C.Y. Li, et al. (2018)

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