Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma

Our plain-English summary of Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma, by K. Hotta, N. Fujimoto (Journal for Immunotherapy of Cancer, 2020).

The study

• Authors: K. Hotta, N. Fujimoto
• Journal: Journal for Immunotherapy of Cancer
• Published: 2020;8(1)
• Type of article: Review
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Platinum-based chemotherapy is commonly used as the standard first-line treatment for unresectable malignant pleural mesothelioma (MPM). However, in recent times, immune-checkpoint inhibitors (ICIs) have led to a paradigm shift. Herein, we review relevant literature and ongoing trials of ICIs used as both first-line and salvage therapies. Specifically, in the Japanese single-arm, phase II trial, the MERIT trial, nivolumab, an antiprogrammed cell death 1 (PD-1) antibody showed favorable efficacy when used as a salvage therapy. Currently, multiple ICI monotherapy or combination therapy trials have been conducted, which could provide further evidence. Among available ICIs, the anti-PD-1 antibody is promising for unresectable MPM, despite the limited efficacy of anti-CTLA4 monotherapy. Ongoing studies will further confirm the potential efficacy of ICIs for MPM, as observed across other malignancies. It is also crucial to identify any clinically useful predictive biomarkers that could reveal ICIs with maximal effects in MPM.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This article was a review, not a new study. The authors reviewed published results and ongoing trials of immune-checkpoint inhibitors for unresectable malignant pleural mesothelioma. They covered these drugs both as a first treatment and as a later (salvage) treatment after chemotherapy. In the Japanese MERIT trial, as the review describes it, nivolumab was given to 34 patients who had already had chemotherapy, and the response rate was 29% (10 of 34). The review states that these results led to approval of nivolumab in Japan. In the DETERMINE trial of 571 previously treated patients, tremelimumab did not significantly prolong survival compared with placebo, with median survival of 7.7 versus 7.3 months. Across the trials listed in the review's table, pneumonitis (lung inflammation) occurred in 2% to 12% of patients. The authors noted that most mesothelioma trials were small and single-arm, and that no clear survival advantage had been shown in randomized trials. The authors concluded that anti-PD-1 antibodies yielded favorable response rates in the salvage setting, and that ongoing studies and useful predictive biomarkers were still needed.

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 published trials and ongoing trials of immune-checkpoint inhibitors
• Who was studied: Published and ongoing clinical trials of immune-checkpoint inhibitors in patients with unresectable malignant pleural mesothelioma, in first-line and salvage settings; the two authors searched for and assessed the studies
• Exposure: Treatment with immune-checkpoint inhibitors (nivolumab, pembrolizumab, avelumab, durvalumab, tremelimumab, ipilimumab), alone or in combination, or added to cisplatin and pemetrexed chemotherapy. This was drug treatment, not asbestos exposure.
• Main results:
  • MERIT trial (reviewed): nivolumab in 34 previously treated patients with malignant pleural mesothelioma had an objective response rate of 29% (10/34). The rate was 40% when tumor PD-L1 expression was 1% or more and 8% when it was below 1%. Median progression-free survival was 6.1 months and median survival time 17.3 months.
  • According to the review, the MERIT results led to approval of nivolumab in Japan for unresectable recurrent pleural mesothelioma
  • DETERMINE trial (reviewed): in 571 previously treated patients with malignant mesothelioma, tremelimumab did not significantly prolong overall survival versus placebo. Median survival time was 7.7 months (tremelimumab) and 7.3 months (placebo), HR 0.92, 95% CI 0.76 to 1.12.
  • MAPS2 trial (reviewed): 125 patients with relapsed malignant pleural mesothelioma received nivolumab plus ipilimumab or nivolumab alone. Disease control rate was 50% and 44%, and objective response rate 28% and 19%, respectively. Grade 3 to 4 adverse events occurred in 26% and 14%, and 3 of 62 combination patients had toxicities that led to death.
  • DREAM trial (reviewed): durvalumab added to cisplatin and pemetrexed in 54 untreated patients with unresectable malignant pleural mesothelioma. Progression-free survival at 6 months was 57%, and the objective response rate was 48%.
  • Across the immune-checkpoint inhibitor trials in the review's Table 1, pneumonitis occurred in 2% to 12% of patients (median 6%)
• The authors' conclusion: The authors concluded that in the salvage setting anti-PD-1 antibodies yielded favorable response rates and that nivolumab is approved in Japan. They also concluded that ongoing studies should further confirm efficacy and that clinically useful predictive biomarkers need to be identified.
• Limitations the authors state:
  • Most prior mesothelioma trials were small and single-arm with response-based endpoints, and no clear survival advantage of immune-checkpoint inhibitors had been shown in randomized trials
  • Most patients with untreated, unresectable mesothelioma do not meet trial eligibility criteria, so trial results must be interpreted cautiously for everyday patients
  • Reported PD-L1 positivity rates come from small studies, so these data may be limited

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Unresectable, Pleural Mesothelioma, Chemotherapy, Nivolumab (Opdivo), Biomarker.

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