Treat it or Leave it: Immuno-Oncology in Mesothelioma Observed by the Eyes of Argus

Our plain-English summary of Treat it or Leave it: Immuno-Oncology in Mesothelioma Observed by the Eyes of Argus, by C.J. de Gooijer, P. Baas (Journal of Thoracic Oncology, 2018).

The study

• Authors: C.J. de Gooijer, P. Baas
• Journal: Journal of Thoracic Oncology
• Published: 2018;13(11):1619-1622
• Type of article: Editorial, Comment
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This editorial commented on a real-world, retrospective study by Metaxas et al. of pembrolizumab as palliative immunotherapy in malignant pleural mesothelioma (MPM). That study had reported an overall response rate of 18.3%, progression-free survival (PFS) of 3.1 months and overall survival (OS) of 7.2 months in 93 patients treated in first-line or beyond. The authors placed these results alongside earlier immunotherapy trials. Small phase I and II studies of pembrolizumab, nivolumab with or without ipilimumab, and tremelimumab had reported promising results, such as a median PFS of 5.4 months and median OS of 18 months in KEYNOTE-028. However, tremelimumab had failed to show superiority over placebo in the randomized phase IIb DETERMINE trial. The authors noted that the real-world pembrolizumab results were close to the DETERMINE placebo arm (PFS 3.1 versus 2.7 months; OS 7.2 versus 7.3 months). They identified limitations of the Metaxas study: it had no control arm, 29% of patients had a performance score of 2, doses varied, response assessment was not standardized, and there was no central radiological review. They described the evidence on PD-L1 expression as a predictor of outcome as controversial. They concluded that immunotherapy use outside clinical trials should be limited, and that ongoing phase III trials with control arms, CheckMate 743 and CONFIRM, were crucial.

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 was an editorial, not a new study. The authors, from the Netherlands Cancer Institute in Amsterdam, commented on a separate retrospective 'real-world' report by Metaxas and colleagues on the immunotherapy drug pembrolizumab in patients with malignant pleural mesothelioma. As the editorial described it, that report covered 93 patients and found an overall response rate of 18.3%, progression-free survival of 3.1 months and overall survival of 7.2 months. The authors compared these figures with the placebo arm of a different trial, DETERMINE (progression-free survival 2.7 months, overall survival 7.3 months), and said the real-world results were close to the placebo results. They noted that the Metaxas report had no control arm, that 29% of its patients had a performance score of 2, that doses varied, and that response assessment was not standardized. The authors concluded that, because the real-world data were close to the historic placebo arm, immunotherapy use outside trials should be limited. They said phase III trials with a control arm were crucial to judge these treatments. The editorial did not address 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: Editorial commenting on a separately published retrospective real-world analysis (Metaxas et al.) and comparing it with other published immunotherapy trials in mesothelioma; no new data were collected
• Who was studied: No population of its own. The editorial discussed the Metaxas et al. report of 93 patients with malignant pleural mesothelioma treated with pembrolizumab in first-line or later treatment (Switzerland and Australia)
• Exposure: Not about asbestos exposure. The treatment discussed was pembrolizumab immunotherapy; in the Metaxas report doses varied from 2 mg/kg every 21 days to 10 mg/kg every 14 days
• Main results:
  • The authors said the Metaxas real-world survival figures for pembrolizumab were close to those of the placebo arm of the separate DETERMINE trial: median progression-free survival 3.1 months versus 2.7 months, and median overall survival 7.2 months versus 7.3 months
  • The authors pointed out that the Metaxas real-world study had no control arm, so the added value of pembrolizumab could not be judged
  • In the Metaxas study, 29% of patients had a performance score of 2, and survival curves were not shown by performance score alone
  • The authors noted that response assessment in the Metaxas study had no central radiological review and response measurement times were not standardized, making comparison of response rates unreliable
  • As reported in the editorial, in the Metaxas multivariate analysis neither tumor histology nor PD-L1 expression remained significantly associated with outcome
  • The authors said ongoing or recently closed phase III trials with a control arm were crucial to evaluate immunotherapy in this population
• The authors' conclusion: The authors concluded that, because the real-world pembrolizumab data were close to the historic placebo arm, immunotherapy use outside of trials should be limited
• Limitations the authors state:
  • The authors acknowledged that comparing results across different trials has significant limitations

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: Mesothelioma, Pembrolizumab (Keytruda), Palliative Care, Immunotherapy, Pleural Mesothelioma, Progression-Free Survival, Overall Survival, Nivolumab (Opdivo).

Related studies

• Immuno-oncology in malignant pleural mesothelioma — P. Baas, M. Disselhorst (2018)
• Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors — S. Hendry, R. Salgado, et al. (2017)
• What can independent research for mesothelioma achieve to treat this orphan disease? — A. Guazzelli, P. Meysami, et al. (2019)
• Closing the stable door before the horse leaves — V. Acton (2015)
• "It sort of hit me like a baseball bat between the eyes": a qualitative study of the psychosocial experiences of mesothelioma patients and carers — S. Girgis, A. Smith, et al. (2019)
• 1987 H. P. Smith award lecture. Eyes for the epidemiologist: the pathologist's role in shaping our understanding of the asbestos-associated diseases — J.E. Craighead (1988)

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