Immune checkpoint inhibitors in malignant pleural mesothelioma

Our plain-English summary of Immune checkpoint inhibitors in malignant pleural mesothelioma, by G.L. Ceresoli, A. Mantovani (The Lancet. Oncology, 2017).

The study

• Authors: G.L. Ceresoli, A. Mantovani
• Journal: The Lancet. Oncology
• Published: 2017;18(5):559-561
• Type of article: Comment
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This invited comment discussed immune checkpoint inhibitors in malignant pleural mesothelioma. Most patients receive first-line chemotherapy with pemetrexed and a platinum agent, and no standard second-line or further-line therapy was available. The authors noted that tremelimumab, an anti-CTLA-4 antibody, had not improved survival in a randomised, double-blind, placebo-controlled phase 2–3 study. Preliminary data on drugs targeting the PD-1 pathway had shown partial responses in around 20% of patients and disease control in 50–80%. They commented on the study by Alley and colleagues in the same issue, in which pembrolizumab was given to 25 patients with pretreated malignant pleural mesothelioma expressing PD-L1. Five (20%) had a partial response and 13 (52%) had disease stabilisation. Median progression-free survival was 5·4 months and median overall survival was 18·0 months. The authors urged caution because the timing between diagnosis and the start of pembrolizumab was not reported, modified RECIST criteria for mesothelioma were not used for the primary analysis, and no central imaging review was done. They concluded that single-agent immunotherapy had proven but limited benefit, possibly because of the disease's complex biology: it does not rank high in mutational load, and its pathogenesis seems to be driven by inflammation. They hypothesised that tumour-associated macrophages contribute to immunosuppression. They suggested that targeting these cells, transforming growth factor β, VISTA or mesenchymal transition might complement PD-1 inhibition in rationally designed combination therapies.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article is a short commentary, not an original study. The authors discussed immune checkpoint inhibitor drugs for malignant pleural mesothelioma and commented on a separate trial by Alley and colleagues published in the same journal issue. In that trial, pembrolizumab was given to 25 previously treated patients whose mesothelioma expressed PD-L1. Of these, 5 patients (20%) had a partial response and 13 (52%) had stable disease. Median progression-free survival was 5.4 months (95% CI 3.4 to 7.5), and median overall survival was 18.0 months (9.4 months to not reached). The authors also noted that tremelimumab had not improved survival in an earlier placebo-controlled study. They said the trial's results should be viewed with caution. The trial did not report the time from diagnosis to treatment, did not use mesothelioma-specific response criteria for its main analysis, and had no central imaging review. The authors concluded that early data suggest single-agent immunotherapy has proven but limited benefit in this disease. They proposed, as a hypothesis, that targeting tumour-associated macrophages might add to PD-1 inhibition. The article does not discuss asbestos exposure.

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: Commentary (invited comment) on another group's clinical trial; no original data
• Who was studied: No population studied by these authors; the commented trial (Alley and colleagues, KEYNOTE-028) treated 25 patients with pretreated malignant pleural mesothelioma expressing PD-L1
• Main results:
  • In Alley and colleagues' trial (not done by these authors), 5 of 25 patients (20%) had a partial response
  • In the same trial, 13 patients (52%) achieved disease stabilisation
  • In the same trial, median progression-free survival was 5.4 months (95% CI 3.4 to 7.5)
  • In the same trial, median overall survival was 18.0 months (9.4 to not reached)
  • The authors noted that tremelimumab, an anti-CTLA-4 antibody, did not improve patient survival in a separate randomised, double-blind, placebo-controlled phase 2–3 study
• The authors' conclusion: The authors concluded that preliminary data suggest single-agent immunotherapy has proven but limited benefit in malignant pleural mesothelioma, possibly because of its complex biology. They hypothesised that myelomonocytic cells such as tumour-associated macrophages may play a major role in immunosuppression, and that targeting them might complement PD-1 inhibition. They said Alley and colleagues' study raises more questions than it answers.
• Limitations the authors state:
  • The authors said the trial's data should be considered with caution
  • The authors noted that Alley and colleagues did not report the time between initial diagnosis and the start of pembrolizumab, an important prognostic factor
  • The authors noted that modified response criteria for mesothelioma were not used for the primary analysis and no central imaging review was done, which makes comparison with other studies difficult
  • The authors' proposed role for macrophages is a hypothesis, not a tested finding

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, Pleural Mesothelioma, Chemotherapy, Pemetrexed (Alimta), Tremelimumab, CTLA-4, Pembrolizumab (Keytruda), PD-L1.

Related studies

• Immune checkpoint inhibitors in malignant pleural mesothelioma: promises and challenges — G.L. Ceresoli, M. Bonomi, et al. (2016)
• Immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): Approaches on special subgroups and unresolved burning questions — J. Remon, N. Vilariño, et al. (2018)
• Immune checkpoint inhibitor associated reactivation of primary membranous nephropathy responsive to rituximab — J.S. Lin, D.Y. Wang, et al. (2020)
• Pre-treatment high-sensitivity troponin T for the short-term prediction of cardiac outcomes in patients on immune checkpoint inhibitors — S. Petricciuolo, M.G. Delle Donne, et al. (2021)
• 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)
• PD-L1 Testing for Immune Checkpoint Inhibitors in Mesothelioma: For Want of Anything Better? — S. Lantuejoul, N. Le Stang, et al. (2017)

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