Emerging New Targets in Systemic Therapy for Malignant Pleural Mesothelioma

Our plain-English summary of Emerging New Targets in Systemic Therapy for Malignant Pleural Mesothelioma, by K.M. Yun, L. Bazhenova (Cancers, 2024).

The study

• Authors: K.M. Yun, L. Bazhenova
• Journal: Cancers
• Published: 2024;16(7)
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a heterogeneous cancer composed of distinct molecular and pathologic subtypes. Unfortunately, MPM is aggressive, and current therapies for advanced, unresectable disease remain limited to cytotoxic chemotherapy and immunotherapy. Our understanding of the genomic landscape of MPM is steadily growing, while the discovery of effective targeted therapies in MPM has advanced more slowly than in other solid tumors. Given the prevalence of alterations in tumor suppressor genes in MPM, it has been challenging to identify actionable targets. However, efforts to characterize the genetic signatures in MPM over the last decade have led to a range of novel targeted therapeutics entering early-phase clinical trials. In this review, we discuss the advancements made thus far in targeted systemic therapies in MPM and the future direction of targeted strategies in patients with advanced MPM.

In plain English

This article was a review by two authors at the Moores Cancer Center at UC San Diego Health. It covered progress in targeted drug therapies for malignant pleural mesothelioma (MPM), which the authors described as arising from the pleural cavity. It did not study new patients or asbestos exposure. Instead, it summarized other researchers' laboratory studies and early clinical trials of drugs aimed at specific molecules or gene changes in mesothelioma, including mesothelin, BAP1, NF2, CDKN2A, MTAP, AXL and ASS1. In the trials described, antibody-based drugs aimed at mesothelin had shown limited effect. A cell therapy called gavo-cel showed an objective response rate of 21% in interim data. Other reviewed trials reported modest results, such as partial responses in 6 of 43 mesothelioma patients given VT3989, and disease control at 12 weeks in 14 of 26 patients given abemaciclib. The authors noted that no targeted drugs were approved for MPM at the time. They concluded that further research was needed to find markers predicting which patients would benefit most from which targeted treatment.

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 clinical review of published preclinical studies and clinical trials
• Who was studied: No new patients were studied. The review covered published and ongoing studies of targeted systemic therapies in patients with advanced malignant pleural mesothelioma, plus related laboratory and animal studies.
• Exposure: Not applicable. The review does not discuss asbestos or any fiber exposure. It covers drug therapies aimed at molecular targets in MPM (mesothelin, BAP1, NF2, CDKN2A, MTAP, AXL, ASS1).
• Main results:
  • In the studies reviewed, antibody-based and antibody-drug conjugate therapies against mesothelin had shown limited efficacy in MPM.
  • Interim data from a phase 1/2 study of gavo-cel (TC-210) in patients with treatment-refractory MPM showed an objective response rate of 21%, median progression-free survival of 5.6 months (unit given in Table 1) and median overall survival of 11.2 months.
  • In a phase 2 trial of olaparib in 23 patients with refractory pleural and peritoneal MPM, 1 patient (4%) had a partial response and 18 (78%) had stable disease.
  • In the MiST1 trial of rucaparib in 26 patients with BAP1- or BRCA1-deficient mesotheliomas, the disease control rate was 58% at 12 weeks and 23% at 24 weeks.
  • In a phase 2 trial of tazemetostat in 74 patients with relapsed or refractory MPM, the objective response rate was 3%. The disease control rate was 51% at 12 weeks and 28% at 24 weeks.
  • In a phase 1 study of VT3989, 6 of the 43 patients with malignant mesothelioma (14%) had a partial response.
  • In the MiST2 trial of abemaciclib in patients with p16ink4A-negative mesothelioma, 14 of 26 patients (54%) achieved disease control at 12 weeks.
  • In the randomized ADAM trial in patients with ASS1-deficient MPM, median progression-free survival was 3.2 months with ADI-PEG20 versus 2.0 months with best-supportive care (p = 0.03; HR 0.56).
  • In the ATOMIC-meso trial in 249 patients with non-epithelioid MPM, median overall survival was 9.3 months with ADI-PEG20 plus chemotherapy versus 7.7 months with chemotherapy alone.
  • At the time of writing, no targeted therapeutics were approved for the treatment of MPM.
• The authors' conclusion: The authors concluded that progress in precision medicine for MPM requires ongoing research to identify predictive biomarkers, so that patients can be matched to the most effective targeted strategy.

Topics

Medical terms in this study, explained in our Lexicon: Systemic Therapy, Pleural Mesothelioma, Unresectable, Chemotherapy, Immunotherapy, Discovery, Tumor Suppressor Gene, Clinical Trial.

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• Pembrolizumab-induced myocarditis in a patient with malignant mesothelioma: plasma exchange as a successful emerging therapy-case report — S.R.I. Schiopu, L. Käsmann, et al. (2021)
• Novel Insights Into Mesothelioma Therapy: Emerging Avenues and Future Prospects — L. Kuryk, G. Rodella, et al. (2022)
• From biology to therapy: current standards and emerging strategies in pleural mesothelioma — J.H.L.T. van Genugten, C.J. de Gooijer, et al. (2026)

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