Novel and Future Treatment Options in Mesothelioma: A Systematic Review

Our plain-English summary of Novel and Future Treatment Options in Mesothelioma: A Systematic Review, by D. Štrbac, V. Dolžan (International Journal of Molecular Sciences, 2022).

The study

• Authors: D. Štrbac, V. Dolžan
• Journal: International Journal of Molecular Sciences
• Published: 2022;23(4)
• Type of article: Systematic review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma is a rare tumor, frequently associated with asbestos exposure, arising from pleura and peritoneum. Traditionally, diagnosis and treatment have been difficult in a clinical setting. The treatment is based on a trimodal approach involving surgery, chemotherapy, and radiotherapy. The introduction of chemotherapy improved the overall survival. However, the regimen of pemetrexed/cisplatin doublet has not been changed as a standard treatment since 2004. Novel combinations of ipilimumab and nivolumab have only been approved for clinical use in late 2020. The aim of this review was to systematically summarize findings on novel treatment options in mesothelioma. We searched available medical databases online, such as PubMed and Clinicaltrials.gov, to systematically review the literature on novel approaches in immunotherapy, vaccines, and Chimeric Antigen Receptor (CAR)-T cell therapy in mesothelioma. We manually screened 1127 articles on PubMed and 450 trials on ClinicalTrials.gov, and 24 papers and 12 clinical trials published in the last ten years were included in this review. Immunotherapy that was swiftly introduced to treat other thoracic malignancies was slow to reach desirable survival endpoints in mesothelioma, possibly due to limited patient numbers. Novel treatment approaches, such as CAR-T cell therapy, are being investigated. As the incidence of mesothelioma is still rising globally, novel treatment options based on a better understanding of the tumor microenvironment and the genetic drivers that modulate it are needed to support future precision-based therapies.

In plain English

This article was a systematic review, not an original study of patients or of asbestos exposure. The authors searched PubMed and ClinicalTrials.gov. They screened 1127 articles and 450 trials and included 24 papers and 12 clinical trials on newer mesothelioma treatments: immunotherapy with checkpoint inhibitors, vaccines, CAR-T cell therapy, and gene-based approaches. Among the studies they described, the CheckMate 743 trial of 713 mainly unresectable patients reported overall survival of 18.1 months with nivolumab plus ipilimumab, compared with 14.1 months with a pemetrexed and carboplatin regimen. The authors wrote that overall response rates in these immunotherapy trials were around 20 to 30%. A vaccine trial (SKOPOS) of 27 patients reported disease control in 87% of patients. All CAR-T cell trials the authors found on ClinicalTrials.gov were still in phase I. Gene-based approaches had been studied only in cell lines and animal models. Results of several trials were still pending. The authors concluded that results of checkpoint inhibitor therapy had been modest. They concluded that understanding the tumor microenvironment and the genetic drivers that modulate it seems to be the future of precision-based therapy in mesothelioma.

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: Systematic review of published papers and registered clinical trials on novel mesothelioma treatments
• Who was studied: 1127 PubMed records and 450 ClinicalTrials.gov trials were screened. 24 papers and 12 clinical trials were included. The PubMed search covered 2000 to 2021. The included studies involved mesothelioma patients, tissue samples, cell lines and animal models.
• Exposure: Not an exposure study. The review covered treatments: checkpoint inhibitors (nivolumab, ipilimumab, pembrolizumab) alone or with chemotherapy, oncolytic viral and vaccine therapies, CAR-T cell therapy, and gene and genetic therapies. Asbestos is mentioned only as background.
• Main results:
  • In the CheckMate 743 trial, as described by the review, 713 primarily unresectable mesothelioma patients had overall survival of 18.1 months with first-line nivolumab/ipilimumab versus 14.1 months with a pemetrexed/carboplatin regimen.
  • In another trial (108 patients per Table 2), the nivolumab/ipilimumab combination had a median overall survival of 15.9 months. Toxicity was higher than with the single agent, and 12-week disease control was seen in 40% of patients in the combination arm.
  • In a phase Ib pembrolizumab trial of 25 patients (Table 2), grade III or above toxicity was 4%. Partial response occurred in 25% of patients and stable disease in 52%.
  • The review stated that the overall response rate in these immunotherapy trials was around 20 to 30%.
  • Three dendritic cell therapy studies reported 20.7% overall survival at five years. The randomized DENIM trial was still recruiting, and its results were pending.
  • In the SKOPOS vaccine trial of 27 patients (TroVax with pemetrexed/cisplatin), disease control was reported in 87% of patients, overall survival was 10.9 months, and progression-free survival was 6.8 months. Results of the NIPU trial (118 patients) and the ONCOS-102 trial were still pending.
  • 11 CAR-T cell mesothelioma trials were found on ClinicalTrials.gov, all in phase I. In one trial, 25 patients with advanced disease received intrapleural CAR-T cells, most also receiving pembrolizumab; the review gives a median overall survival of 23.9 months 'in these patients'. A 15-patient trial in several solid cancers showed no clinical benefit beyond stable disease.
  • Gene and genetic therapy approaches (miRNA, shRNA, splicing modulators) had been studied only in mesothelioma cell lines and animal models.
• The authors' conclusion: The authors concluded that results of checkpoint inhibitor therapy had been modest. They concluded that understanding the mesothelioma microenvironment and its genetic drivers seems to be the future of precision-based therapy. They also wrote that the trials so far suggest CAR-T cell therapy is safe in mesothelioma but that its efficacy needs further evaluation.
• Limitations the authors state:
  • The authors stated that the text and tables focused on clinical trials that had published their data. Information on other trials was placed in supplementary tables.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Systematic Review, Asbestos Exposure, Pleura, Peritoneum, Chemotherapy, Overall Survival, Pemetrexed (Alimta).

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