Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma

Our plain-English summary of Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma, by E. Vita, A. Stefani, M. Di Salvatore, et al (Journal of Clinical Medicine, 2021).

The study

• Authors: E. Vita, A. Stefani, M. Di Salvatore, M. Chiappetta, F. Lococo, S. Margaritora, G. Tortora, E. Bria
• Journal: Journal of Clinical Medicine
• Published: 2021;10(11)
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by very poor prognosis and lack of treatment options. Immunotherapy has rapidly emerged as an effective tool for MPM, particularly for tumors of non-epithelioid histology. At the same time, comprehensive genomic sequencing may open the way to new-generation targeted-drugs able to hit specific MPM molecular vulnerabilities. These innovations will possibly enrich, but also dramatically complicate, the elucidation of treatment algorithms. Multidisciplinary integration is urgently needed.

In plain English

This article was a narrative review of newer treatment options for malignant pleural mesothelioma (MPM). It did not study patients directly. It summarized published and ongoing clinical trials of three approaches: immunotherapy, drugs aimed at tumors that have lost tumor-suppressor genes such as BAP1, and drugs that block blood-vessel growth. The introduction stated that asbestos exposure, usually in the workplace, is the leading cause of MPM, but no fiber types were discussed. The review reported that in the CheckMate 743 trial, median overall survival was 18.1 months with nivolumab plus ipilimumab versus 14.1 months with chemotherapy (HR 0.74). In non-epithelioid tumors the figures were 18.1 versus 8.8 months. In epithelioid tumors they were 18.7 versus 16.5 months (HR 0.86, 95% CI 0.69 to 1.08). The authors noted that this trial was not powered to compare these subgroups. In the CONFIRM trial, median survival in relapsed MPM was 9.2 months with nivolumab versus 6.6 months with placebo. In the DETERMINE trial, tremelimumab showed no significant survival difference from placebo. The authors concluded that upfront immunotherapy marks a significant milestone for non-epithelioid MPM.

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 of treatments for malignant pleural mesothelioma
• Who was studied: No patients were studied directly. The review covered selected published and ongoing clinical trials of immunotherapy and targeted drugs in MPM, listed in two tables.
• Exposure: This is not an exposure study; it reviews treatments. The introduction states that asbestos exposure, usually occupational, is the leading cause of MPM. No fiber types are named.
• Main results:
  • As reported in this review, the CheckMate 743 trial (605 untreated patients) found median overall survival of 18.1 months with nivolumab plus ipilimumab versus 14.1 months with platinum-pemetrexed chemotherapy (HR 0.74, p = 0.002).
  • In CheckMate 743's non-epithelioid subgroup, median overall survival was 18.1 months with nivolumab plus ipilimumab versus 8.8 months with chemotherapy (HR 0.46, 95% CI 0.31 to 0.68).
  • In CheckMate 743's epithelioid subgroup, median overall survival was 18.7 months with nivolumab plus ipilimumab versus 16.5 months with chemotherapy (HR 0.86, 95% CI 0.69 to 1.08). The authors described this as not showing clear superiority.
  • In the CONFIRM trial (332 patients with relapsed MPM), median overall survival was 9.2 months with nivolumab versus 6.6 months with placebo (HR 0.72, p = 0.02).
  • In the DETERMINE trial (571 pre-treated patients), there was no significant survival difference: median overall survival was 7.7 months with tremelimumab versus 7.3 months with placebo (p = 0.408).
  • In the MiST1 trial of rucaparib in relapsed BAP1-deficient or BRCA1-deficient mesothelioma, disease control at 12 weeks was 58% (15 of 26 patients).
  • In a phase II study of tazemetostat in relapsed or refractory MPM with BAP1 inactivation, disease control at 12 weeks was 47% (35 of 74 patients).
  • In the MAPS trial, adding bevacizumab to cisplatin-pemetrexed only slightly prolonged median overall survival (18.8 vs. 16.1 months), with more grade 3 to 4 toxicities.
• The authors' conclusion: The authors concluded that upfront immunotherapy marks a significant milestone for non-epithelioid MPM, which is usually refractory to chemotherapy.
• Limitations the authors state:
  • The authors noted that CheckMate 743 was not powered to detect differences between the epithelioid and non-epithelioid subgroups.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Immunotherapy, Non-epithelioid, Histology.

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