Immunological checkpoint inhibitors enter adolescence

Our plain-English summary of Immunological checkpoint inhibitors enter adolescence, by A.K. Nowak (The Lancet. Oncology, 2013).

The study

• Author: A.K. Nowak
• Journal: The Lancet. Oncology
• Published: 2013;14(11):1035-1037
• Type of article: Letter, Comment
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this invited comment, the author discussed the trial by Calabrò and colleagues, published in the same issue, which was described as the first clinical trial of an immunological checkpoint inhibitor in malignant mesothelioma. The author first explained how CTLA4 blockade reduces negative regulatory signals on T cells, so that these drugs have potential activity against cancers of any origin. In the trial, all participants had progressed after standard chemotherapy and received tremelimumab. Two of 29 patients had durable partial responses and seven had prolonged stable disease, giving a disease control rate of 31%. Median progression-free survival was 6.2 months (95% CI 1.3–11.1), and almost 40% of participants were alive at 2 years. One participant had progression followed by a lengthy partial response, which the author said suggested a need for immune response criteria in future trials. The study also assessed peripheral blood biomarkers and found that an increase in circulating CD4-positive, ICOS-positive T cells after treatment was a potential biomarker of response, which required further validation. The author cautioned that drawing conclusions about efficacy from an uncontrolled phase 2 study was presumptuous, but called the results encouraging. She concluded that the study provided a solid foundation for a large randomised phase 2 trial of tremelimumab in mesothelioma (NCT01843374). She also noted open questions about how tremelimumab compares with ipilimumab and about combinations with other 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 author discussed a trial by Luana Calabrò and colleagues, published in the same journal and described as the first clinical trial of an immunological checkpoint inhibitor in malignant mesothelioma. That trial tested tremelimumab, an antibody that blocks a T-cell regulator called CTLA4, in patients whose disease had progressed after standard chemotherapy. As the author summarised it, two of 29 patients had durable partial responses and seven more had prolonged stable disease, giving a disease control rate of 31%. Median progression-free survival was 6.2 months (95% CI 1.3 to 11.1), and almost 40% of participants were alive at 2 years. The trial also suggested a possible blood marker of response: a rise in activated CD4-positive, ICOS-positive T cells after treatment. The author cautioned that drawing conclusions about effectiveness from an uncontrolled phase 2 study is presumptuous, and that the blood marker needs validation in a large trial. Even so, the author called the results encouraging and better than expected for this population. The author concluded that the trial provides a foundation for a larger randomised phase 2 study now recruiting. The commentary 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 (editorial comment) on a separately published open-label, single-arm phase 2 trial by Calabrò and colleagues
• Who was studied: The commented-on trial enrolled 29 patients with malignant mesothelioma whose disease had progressed after standard chemotherapy. Location and dates are not given in this commentary.
• Exposure: No asbestos exposure is discussed. The exposure is treatment with tremelimumab, a monoclonal antibody (IgG2) that blocks CTLA4.
• Main results:
  • As reported by the author for the Calabrò trial: 2 of 29 patients had durable partial responses and 7 more had prolonged stable disease, a disease control rate of 31%. Median progression-free survival was 6.2 months (95% CI 1.3 to 11.1).
  • Almost 40% of trial participants were alive at 2 years.
  • In the author's view, the progression-free survival and 2-year survival results were better than expected for this population.
  • One trial participant had disease progression followed by a lengthy partial response.
  • The trial's blood testing suggested a possible use of the rise in circulating CD4-positive, ICOS-positive T cells after treatment as a biomarker of response.
• The authors' conclusion: The author concluded that the results were encouraging, and that the trial provides a solid foundation for testing tremelimumab in a large randomised phase 2 mesothelioma study now recruiting (NCT01843374).
• Limitations the authors state:
  • The author stated that drawing conclusions about efficacy from an uncontrolled phase 2 study is presumptuous.
  • The author stated that the biomarker findings require further validation within a large trial.
  • The author noted that measuring response in mesothelioma is difficult, and that it is unclear how immune response criteria might be applied to it.

Topics

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

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Clinical Trial, Malignant Mesothelioma, Chemotherapy, Tremelimumab, Progression-Free Survival, Biomarker, Mesothelioma.

Related studies

• Biomarkers for immune checkpoint inhibitors — L.A. Lievense, J.P. Hegmans, et al. (2014)
• Biomarkers for immune checkpoint inhibitors--authors' reply — L. Calabrò, M. Maio (2014)
• Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial — L. Calabrò, A. Morra, et al. (2013)
• A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma — W.S. Lam, J. Creaney, et al. (2020)
• Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study — L. Calabrò, A. Morra, et al. (2015)
• Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial — M. Maio, A. Scherpereel, et al. (2017)

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