The Current Treatment Landscape of Malignant Pleural Mesothelioma and Future Directions

Our plain-English summary of The Current Treatment Landscape of Malignant Pleural Mesothelioma and Future Directions, by B. Bertin, M. Zugman, G. Schvartsman (Cancers, 2023).

The study

• Authors: B. Bertin, M. Zugman, G. Schvartsman
• Journal: Cancers
• Published: 2023;15(24)
• Type of article: Review
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The incidence of malignant pleural mesothelioma is expected to increase globally. New treatment options for this malignancy are eagerly awaited to improve the survival and quality of life of patients. The present article highlights the results of recent advances in this field, analyzing data from several relevant trials. The heterogeneous tumor microenvironment and biology, together with the low mutational burden, pose a challenge for treating such tumors. So far, no single biomarker has been soundly correlated with targeted therapy development; thus, combination strategies are often required to improve outcomes. Locally applied vaccines, the expansion of genetically engineered immune cell populations such as T cells, the blockage of immune checkpoints that inhibit anti-tumorigenic responses and chemoimmunotherapy are among the most promising options expected to change the mesothelioma treatment landscape.

In plain English

This article was a narrative review of treatments for malignant pleural mesothelioma, a cancer of the pleural lining that the authors described as highly associated with asbestos exposure. It did not collect new patient data. Instead it summarized published and ongoing clinical trials of chemotherapy, immunotherapy, combined chemotherapy and immunotherapy, targeted drugs, cell therapies and tumor-treating fields. As reported in the review, the CheckMate 743 trial of 600 patients found a median overall survival of 18.1 months with nivolumab plus ipilimumab, compared with 14.1 months with chemotherapy (HR 0.73; 95% CI 0.61 to 0.87). The IND227 trial found a median overall survival of 17.3 months when pembrolizumab was added to chemotherapy, compared with 16.1 months with chemotherapy alone (HR 0.79; 95% CI 0.64 to 0.98). The review also reported that the MARS2 trial did not show an advantage for surgery over chemotherapy alone. It described early trials of drugs aimed at gene changes such as BAP1 loss. The authors concluded that this complex and varied disease may have a greater chance of successful treatment with combined approaches. They did not state limitations of their own review.

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 and other published research on treatment of malignant pleural mesothelioma
• Who was studied: No study population of its own; the review summarized published and ongoing clinical trials in patients with malignant pleural mesothelioma
• Exposure: Not an exposure study; the review concerns treatments. In its introduction, citing earlier work, it describes malignant pleural mesothelioma as highly associated with asbestos exposure (over 80% of cases)
• Main results:
  • As reported in the review, in the CheckMate 743 trial, patients given nivolumab plus ipilimumab had a median overall survival of 18.1 months, compared with 14.1 months for patients given chemotherapy (HR: 0.73; 95% CI: 0.61 to 0.87). The trial randomized 600 patients.
  • As reported in the review, four-year overall survival rates in CheckMate 743 were 17% for nivolumab plus ipilimumab and 11% for chemotherapy.
  • As reported in the review, in the IND227 trial, adding pembrolizumab to pemetrexed-platinum chemotherapy gave a median overall survival of 17.3 months, compared with 16.1 months in the chemotherapy-only arm (HR: 0.79; 95% CI: 0.64 to 0.98; p = 0.0324).
  • As reported in the review, the 2003 EMPHACIS trial showed that pemetrexed with cisplatin increased median overall survival by 2 to 3 months compared with cisplatin alone.
  • As reported in the review, the randomized phase 3 MARS2 trial did not show an advantage for patients who had surgery compared with those who had chemotherapy alone.
  • As reported in the review, in the MiST1 trial of rucaparib in 26 patients with relapsed mesothelioma with BAP1 or BRCA-1 deficiency, the disease control rate was 58% at 12 weeks and 23% at 24 weeks.
  • As reported in the review, in a phase II trial of tazemetostat in relapsed patients with inactivated BAP1, the disease control rate was 54% at week 12 and 28% at 24 weeks.
• The authors' conclusion: The authors concluded that, because the disease is complex and heterogeneous, combined treatment approaches may have a greater chance of success. They also noted that new biomarker-directed therapies are being developed.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Quality of Life, Tumor Microenvironment, Biomarker, Targeted Therapy, Mesothelioma.

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