CTLA4 blockade in patients with malignant mesothelioma

Our plain-English summary of CTLA4 blockade in patients with malignant mesothelioma, by B.M. Burt (The Lancet. Respiratory Medicine, 2015).

The study

• Author: B.M. Burt
• Journal: The Lancet. Respiratory Medicine
• Published: 2015;3(4):261-3
• Type of article: Comment
• Read it: PubMed · Publisher

In plain English

This is a short commentary, not an original study. The author discussed a phase 2 trial by Calabrò and colleagues (MESOT-TREM-2012). In that trial, 29 patients with advanced mesothelioma (28 pleural, one peritoneal) received an intensified schedule of tremelimumab, an antibody that blocks the immune checkpoint CTLA4. All of them had progressed after one platinum-based chemotherapy regimen. As the commentary described it, the trial only just met its primary endpoint of four patients achieving an immune-related objective response. Grade 1–2 treatment-related side effects occurred in 26 (90%) of 29 patients and grade 3–4 in two (7%). Disease control was reached in 11 (38%) of 29 patients, compared with nine (31%) of 29 in the same investigators' earlier, less intensive trial. Median overall survival was 11.3 versus 10.7 months. The author noted that it is difficult to determine conclusively from single-arm data whether the drug has clinically significant activity, and that the data cannot show whether the intensified schedule works better. The author concluded that CTLA4 checkpoint inhibition holds promise. The commentary 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: Commentary (editorial comment) on another group's published open-label, single-arm, phase 2 trial (Calabrò and colleagues, MESOT-TREM-2012); not original research by the author
• Who was studied: In the trial discussed: 29 patients with advanced mesothelioma (28 pleural, 1 peritoneal), all of whom had progressed after one platinum-based chemotherapy regimen
• Exposure: No asbestos exposure is discussed. The intervention in the trial discussed was tremelimumab, an anti-CTLA4 monoclonal antibody, at 10 mg/kg once every 4 weeks for six doses, then every 12 weeks
• Main results:
  • In the trial discussed (MESOT-TREM-2012), the primary endpoint of four patients achieving an immune-related objective response was only just met
  • In MESOT-TREM-2012, grade 1–2 treatment-related adverse events occurred in 26 (90%) of 29 patients and grade 3–4 in two (7%) patients
  • Disease control was achieved by 11 (38%) of 29 patients in MESOT-TREM-2012, compared with nine (31%) of 29 in the earlier, less intensive MESOT-TREM-2008 trial (the trailing 3 and 2 in the quote are reference numbers)
  • Median overall survival was 11.3 months in MESOT-TREM-2012 and 10.7 months in MESOT-TREM-2008 (the trailing 3 and 2 in the quote are reference numbers)
  • In the first 14 patients of MESOT-TREM-2012, pharmacokinetics improved: most patients kept tremelimumab concentrations at or above the target over the whole dosing interval
• The authors' conclusion: The author concluded that strategies to enhance anti-tumour immune responses, such as CTLA4 checkpoint inhibition, hold promise for improving outcomes in malignant mesothelioma
• Limitations the authors state:
  • The author stated that whether tremelimumab has clinically significant activity is difficult to determine conclusively from single-arm trial data
  • The author stated that the available data cannot show whether the intensified schedule gives better clinical activity than the less intensive schedule

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: Malignant Mesothelioma.

Related studies

• CTLA4 blockade in mesothelioma: finally a competing strategy over cytotoxic/target therapy? — L. Calabrò, G.L. Ceresoli, et al. (2015)
• Synergistic effect of CTLA-4 blockade and cancer chemotherapy in the induction of anti-tumor immunity — W.J. Lesterhuis, J. Salmons, et al. (2013)
• Clinical studies with anti-CTLA-4 antibodies in non-melanoma indications — L. Calabrò, R. Danielli, et al. (2010)
• Anti-CTLA-4 therapy for malignant mesothelioma — A. Guazzelli, E. Bakker, et al. (2017)
• Immune checkpoint blockade in malignant mesothelioma — L. Calabrò, M. Maio (2015)
• CTLA-4 blockade in mesothelioma: ineffective or reason for optimism? — A. Thomas, R. Hassan (2017)

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