An Update on Emerging Therapeutic Options for Malignant Pleural Mesothelioma

Our plain-English summary of An Update on Emerging Therapeutic Options for Malignant Pleural Mesothelioma, by A. Davis, H. Ke, S. Kao, et al (Lung Cancer, 2022).

The study

• Authors: A. Davis, H. Ke, S. Kao, N. Pavlakis
• Journal: Lung Cancer
• Published: 2022;13:1-12
• Type of article: Review
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The treatment paradigm for malignant pleural mesothelioma (MPM) has changed little in the last 18 years. Radical intent treatment, consisting of surgical resection, radiotherapy and chemotherapy, has been offered to a highly select few; however, there is little randomised evidence to validate this approach. Prior to 2020 chemotherapy with platinum and an anti-folate was the only intervention with randomised evidence to demonstrate improved overall survival (OS) in MPM. No systemic therapy had been demonstrated to improve OS in the second line setting until 2020. The publication of the Checkmate 743 trial in 2021 demonstrated a survival benefit of combination immunotherapy over standard chemotherapy in newly diagnosed patients with MPM. This finding was shortly followed by the CONFIRM trial which demonstrates a modest but significant survival benefit of second line nivolumab versus placebo in patients having previously received standard chemotherapy. The results of these trials, recent biomarker directed therapy and chemotherapy adjuncts are discussed within this review. The integration of immunotherapy for the few patients in whom radical surgical therapy is intended is currently the subject of clinical trials and offers the prospect of improving outcomes in this rare but devastating disease.

© 2022 Davis et al.

In plain English

This article was a review, not a new study. The authors summarised trials of treatments for malignant pleural mesothelioma: surgery, radiotherapy, chemotherapy, immunotherapy and targeted drugs. They described the MARS trial as showing no overall survival benefit for extrapleural pneumonectomy, while noting criticism that it was underpowered. In the Checkmate 743 trial of 605 previously untreated patients with unresectable disease, median overall survival was longer with ipilimumab plus nivolumab than with platinum plus pemetrexed chemotherapy (18.1 versus 14.1 months). The benefit appeared in patients with non-epithelioid tumours (18.1 versus 8.8 months) but was not statistically significant for epithelioid tumours. The trial was not powered to compare these subgroups. For previously treated patients, the CONFIRM trial reported median survival of 9.2 months with nivolumab versus 6.6 months with placebo. PROMISE-Meso found no difference in median survival between pembrolizumab and chemotherapy. The authors concluded that Checkmate 743 established a role for combination immunotherapy. They wrote that it remains to be seen whether it, or chemotherapy combined with immunotherapy, becomes standard for all patients.

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 treatment for malignant pleural mesothelioma
• Who was studied: No new patients were studied. The review covered published trials in patients with malignant pleural mesothelioma (MPM).
• Exposure: Not an asbestos exposure study. The review examined treatments: surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapy. As background, citing other work, it notes that most MPM cases are related to asbestos exposure.
• Main results:
  • MARS trial (reviewed): in patients who had completed neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) showed no overall survival benefit. Median OS was 14.4 months with EPP versus 19.5 months without (HR 1.90, 95% CI 0.92–3.93).
  • Vogelzang et al trial (reviewed): adding pemetrexed to cisplatin improved median OS, 12.1 versus 9.3 months (HR 0.77, p = 0.02).
  • MAPS trial (reviewed): adding bevacizumab to cisplatin and pemetrexed improved median OS, 18.8 versus 16.1 months (HR 0.77, p = 0.0167).
  • Checkmate 743 trial (reviewed), 605 treatment-naive patients with unresectable MPM: at interim analysis, median OS was 18.1 months with ipilimumab plus nivolumab versus 14.1 months with platinum plus pemetrexed (HR 0.74, 96.6% CI 0.60–0.91, p = 0.002).
  • Checkmate 743 subgroups. Patients with non-epithelioid histology had improved median OS with combination immunotherapy: 18.1 versus 8.8 months (HR 0.46, 95% CI 0.31–0.68). Patients with epithelioid histology showed no statistical benefit: 18.7 versus 16.5 months (HR 0.86, 95% CI 0.69–1.08).
  • CONFIRM trial (reviewed), previously treated patients: median OS, described as immature, was 9.2 months with nivolumab versus 6.6 months with placebo (HR 0.72, 95% CI 0.55–0.94, p = 0.018).
  • PROMISE-Meso trial (reviewed), 144 pre-treated patients: no difference in median OS for pembrolizumab versus chemotherapy, 10.7 versus 12.4 months (HR 1.12, 95% CI 0.74–1.69, p = 0.59).
• The authors' conclusion: The authors concluded that the Checkmate 743 trial established a role for combination immunotherapy in treating MPM. Whether combination immunotherapy or chemoimmunotherapy becomes the dominant approach for all patients remains to be seen.
• Limitations the authors state:
  • The authors state that randomised evidence for routine surgery to achieve macroscopic complete resection is lacking, pending the MARS2 trial.
  • The authors note that the MARS trial was underpowered to assess overall survival.
  • The authors note that Checkmate 743 was not powered to show a difference between the epithelioid and non-epithelioid subgroups.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Surgical Resection, Chemotherapy, Overall Survival, Systemic Therapy, CheckMate 743, Immunotherapy, CONFIRM Trial.

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