Immune checkpoint inhibitors in malignant pleural mesothelioma: promises and challenges

Our plain-English summary of Immune checkpoint inhibitors in malignant pleural mesothelioma: promises and challenges, by G.L. Ceresoli, M. Bonomi, M.G. Sauta (Expert Review of Anticancer Therapy, 2016).

The study

• Authors: G.L. Ceresoli, M. Bonomi, M.G. Sauta
• Journal: Expert Review of Anticancer Therapy
• Published: 2016;16(7):673-5
• Type of article: Editorial
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This short editorial reported no new patient data. The authors reviewed other researchers' trials of immune checkpoint inhibitor drugs for malignant pleural mesothelioma, a cancer whose incidence they described as rising because of widespread past exposure to asbestos. In two small phase II trials of tremelimumab, 2 of 29 and 4 of 29 patients had partial responses. A later placebo-controlled trial of tremelimumab (DETERMINE) failed to achieve its primary endpoint. In a phase Ib study of pembrolizumab in PD-L1-positive tumors, 25 previously treated malignant pleural mesothelioma patients had an objective response rate of 28%. In a phase Ib study of avelumab in 20 patients with unresectable pleural or peritoneal mesothelioma that had progressed after platinum and pemetrexed chemotherapy, 3 (15%) had a durable partial response. The authors said that a predictive marker to select patients was still needed. They also noted that these drugs can cause immune-related side effects that may become life threatening if not anticipated and managed. The authors concluded that checkpoint inhibition seemed a promising strategy, but that results were still very preliminary, most trials were ongoing, and further biomarker studies were required.

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 (commentary reviewing other researchers' trials; no original data)
• Who was studied: No study population of its own. The editorial discussed trials by other researchers in patients with unresectable malignant pleural mesothelioma (MPM); some of those trials also included peritoneal mesothelioma.
• Exposure: Immune checkpoint inhibitor drugs (tremelimumab, pembrolizumab, avelumab, nivolumab, ipilimumab, durvalumab). Asbestos was not studied. It was mentioned only as the reason the authors gave for rising MPM incidence.
• Main results:
  • In the first of two earlier phase II tremelimumab trials (another group's study), the disease control rate was 31%.
  • In the second tremelimumab trial (another group's study), 4 of 29 patients had a partial response (14%) and 11 had stable disease, for a disease control rate of 52%.
  • The randomized, placebo-controlled DETERMINE trial of tremelimumab in unresectable malignant pleural or peritoneal mesothelioma failed to achieve its primary endpoint of improving overall survival.
  • In the phase IB KEYNOTE-028 study in PD-L1-positive solid tumors (another group's study), 25 MPM patients received pembrolizumab. The objective response rate was 28% and the disease control rate was 76%.
  • The KEYNOTE-028 mesothelioma patients had already been treated before entering the study.
  • A phase Ib avelumab study (another group's study) enrolled 20 patients with unresectable pleural or peritoneal mesothelioma that had progressed after platinum and pemetrexed chemotherapy.
  • In that avelumab study, 3 of the 20 patients (15%) had a durable partial response and 9 more had stable disease.
  • The authors noted that immune-related side effects, though rarely severe, can become life threatening if not anticipated and managed appropriately.
• The authors' conclusion: The authors concluded that immune checkpoint inhibition seems a promising therapeutic strategy in MPM.
• Limitations the authors state:
  • The authors stated that results are still very preliminary and most trials are still ongoing.
  • The authors stated that a predictive biomarker to guide patient selection is needed, and that further biomarker studies are required.
  • The authors noted that the pembrolizumab KEYNOTE-028 analysis of PD-L1 expression was conducted in a very small sample.

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.

Related studies

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• 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)
• Immune checkpoint inhibitors a new player in the therapeutic game of mesothelioma: New reality with new challenges — K. Parikh, L.E.L. Hendriks, et al. (2021)
• Immune checkpoint therapy of mesothelioma: Pre-clinical bases and clinical evidences — L. Calabrò, G.L. Ceresoli, et al. (2017)
• Moving Immune Checkpoint Blockade in Thoracic Tumors beyond NSCLC — F. Facchinetti, A. Marabelle, et al. (2016)

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