Immune checkpoint inhibitors a new player in the therapeutic game of mesothelioma: New reality with new challenges

Our plain-English summary of Immune checkpoint inhibitors a new player in the therapeutic game of mesothelioma: New reality with new challenges, by K. Parikh, L.E.L. Hendriks, P. Bironzo, et al (Cancer Treatment Reviews, 2021).

The study

• Authors: K. Parikh, L.E.L. Hendriks, P. Bironzo, J. Remon
• Journal: Cancer Treatment Reviews
• Published: 2021;99:102250
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a rare and orphan thoracic malignancy, with a poor prognosis as the majority of patients are diagnosed with unresectable MPM, with no significant improvements in the therapeutic strategy for over a decade. However, the recent approval of immune checkpoint inhibitors (ICI) in treatment-naïve patients with unresectable MPM marks a significant step forward and hope for the treatment of this disease. In this narrative review, we discuss the biological rationale to use ICI in the treatment of MPM. We summarize the current evidence for the efficacy of ICI in MPM and discuss several unresolved challenges regarding the use of ICI in this disease, such as the best upfront immune approach in MPM (ICI versus ICI plus chemotherapy), the optimal sequential treatment strategy according to the first-line treatment, and the potential role of predictive biomarkers.

Copyright © 2021 Elsevier Ltd. All rights reserved.

In plain English

This narrative review, not a new study, summarized published trials of immune checkpoint inhibitors, drugs that help the immune system attack cancer, in malignant pleural mesothelioma (MPM). Asbestos appeared as background on how the disease develops, and the authors proposed that asbestos exposure may contribute to a high neoantigen burden that could help these drugs work in MPM. In CheckMate 743, 605 patients with unresectable MPM were randomly assigned to nivolumab plus ipilimumab (303) or platinum plus pemetrexed chemotherapy (302). Median overall survival was 18.1 versus 14.1 months (HR 0.74, 96.6% CI 0.60 to 0.91), with a larger difference in non-epithelioid than epithelioid disease. For previously treated patients, the CONFIRM trial reported longer survival with nivolumab than placebo (9.2 vs. 6.6 months, data still immature). The PROMISE trial reported that pembrolizumab did not improve survival over chemotherapy. Two single-arm trials of durvalumab plus chemotherapy reported median survival of 18.4 to 20.4 months. The authors noted that comparisons across trials need caution. The authors concluded that these drugs shifted treatment of unresectable MPM, making longer survival possible for a subgroup.

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: Narrative review of published clinical trials and real-world cohorts of immune checkpoint inhibitors in malignant pleural mesothelioma; no search method or total count of studies given
• Who was studied: Patients with malignant pleural mesothelioma (MPM), mostly unresectable, enrolled in the trials and real-world cohorts reviewed. The cohorts covered both untreated and previously treated patients.
• Exposure: Not an asbestos exposure study. What was reviewed was treatment with immune checkpoint inhibitors (nivolumab, ipilimumab, pembrolizumab, durvalumab, avelumab, tremelimumab), alone or with chemotherapy. Asbestos is mentioned in two places, and no fiber types are named. The first is background on how mesothelioma develops. The second is a proposed explanation, not a finding: the authors suggest asbestos exposure, together with germline mutations, may contribute to a high neoantigen burden that could account for these drugs working in MPM.
• Main results:
  • CheckMate 743 trial (as summarized by the review), first-line unresectable MPM: median overall survival was 18.1 months with nivolumab plus ipilimumab versus 14.1 months with platinum plus pemetrexed (HR 0.74, 96.6% CI 0.60–0.91).
  • CheckMate 743, non-epithelioid histology: median overall survival was 18.1 months with nivolumab plus ipilimumab versus 8.8 months with chemotherapy (HR 0.46, 95% CI 0.31–0.68).
  • CheckMate 743, epithelioid subtype: the authors stated that the trial did not suggest superiority of nivolumab plus ipilimumab over chemotherapy in this group (HR 0.86, 95% CI 0.69–1.08).
  • CheckMate 743, PD-L1 negative tumors: median overall survival was 17.3 months with nivolumab plus ipilimumab versus 16.5 months with chemotherapy (HR 0.94, 95% CI 0.62–1.40).
  • CONFIRM trial, 332 previously treated MPM patients randomized 2:1 to nivolumab or placebo: overall survival was 9.2 months with nivolumab versus 6.6 months with placebo (HR 0.72; 95% CI 0.55–0.94). The data were described as still immature.
  • PROMISE trial, 144 previously treated MPM patients: pembrolizumab did not improve overall survival over single-agent chemotherapy (10.7 vs. 12.4 months; HR 1.12, 95% CI 0.74–1.69).
  • DREAM and PrE0505 single-arm phase 2 trials, durvalumab plus platinum and pemetrexed in untreated unresectable MPM: response rate about 50%, median progression-free survival about 7 months, and median overall survival 18.4–20.4 months.
• The authors' conclusion: The authors concluded that immune checkpoint inhibitors shifted the treatment paradigm in unresectable MPM, making prolonged overall survival possible for a subgroup of patients.
• Limitations the authors state:
  • The authors cautioned that comparing results across different trials should be done with caution.
  • The authors noted that results from early (phase Ib) trials of previously treated patients must be interpreted cautiously, because those patients may have been overselected.

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, Mesothelioma, Pleural Mesothelioma, Prognosis, Unresectable, Chemotherapy, Biomarker.

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