Optimal Therapy of Advanced Stage Mesothelioma

Our plain-English summary of Optimal Therapy of Advanced Stage Mesothelioma, by M.M.J. Disselhorst, S.J.A. Burgers, P. Baas (Current Treatment Options in Oncology, 2017).

The study

• Authors: M.M.J. Disselhorst, S.J.A. Burgers, P. Baas
• Journal: Current Treatment Options in Oncology
• Published: 2017;18(8):48
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The optimal treatment of patients with advanced malignant pleural mesothelioma (MPM) has not yet been discovered. With the aid of an increased insight in the molecular pathways and the development of combinations of Immuno-Oncology (IO), drugs new therapies are available. The personalization of treatment by cell cultures and pathway analysis attracts more attention nowadays. It is conceivable that in the near future the treatment of patients with MPM will consist of a combination of IO drugs or specific pathway inhibitors.

In plain English

This article is a review and opinion piece on treating advanced malignant pleural mesothelioma (MPM). The authors write that MPM has a well-documented causal relation with asbestos exposure. They did not run a study of their own; they summarized published and ongoing treatment trials.

The results they described came from other studies. In a French trial, adding bevacizumab to standard care raised median overall survival from 16.1 to 18.8 months. Preliminary data on adding nintedanib to cisplatin and pemetrexed showed progression-free survival rising from 5.7 to 9.4 months. In patients whose tumors lacked the enzyme ASS1, the drug ADI-PEG20 gave progression-free survival of 3.2 months, compared with 2.0 months for supportive care alone.

The authors wrote that no second-line treatment had a proven clinical benefit. Single PD-1 blocking drugs produced responses in around 25% of patients, and a large phase III trial of tremelimumab was negative. They also discussed anti-mesothelin drugs and BAP1 as a possible treatment target. The authors concluded that future MPM treatment may combine immuno-oncology drugs or specific pathway inhibitors.

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 with an opinion statement; the authors report no study of their own
• Who was studied: Patients with advanced malignant pleural mesothelioma, as studied in the trials and case series the review discusses
• Exposure: Asbestos exposure was not studied. The article reviews treatments: chemotherapy, bevacizumab, nintedanib, maintenance therapy, ADI-PEG20, immune checkpoint inhibitors, anti-mesothelin agents and BAP1-directed approaches. Asbestos is mentioned only as background, citing another source.
• Main results:
  • In the French intergroup trial the authors cite, median overall survival was 16.1 months in the control group and 18.8 months in the bevacizumab group (HR 0.77 (0.62–0.95); p = 0.0167)
  • In preliminary data the authors cite on adding nintedanib to cisplatin/pemetrexed, progression-free survival rose from 5.7 to 9.4 months (HR 0.56 (0.34–0.91), p = 0.017)
  • In a cited randomized phase 2 trial, 68 of 201 patients had ASS1 deficiency. Progression-free survival was 3.2 months with ADI-PEG20 versus 2.0 months in the control arm, and no partial or complete responses were seen.
  • The authors stated that no second-line treatment had a proven clinical benefit
  • In the conference reports the authors cite on single-agent PD-1 blockers, responses were around 25%; a large phase III study of tremelimumab was negative
  • In a cited Mayo Clinic case series, 42 (40%) of 106 eligible patients expressed PD-L1, and PD-L1 positive patients had significantly shorter survival (multivariate risk ratio 1.71, 95% CI 1.03–2.78; p = 0.04)
  • In a cited 222-patient randomized phase III study, switch maintenance with thalidomide did not improve progression-free or overall survival
• The authors' conclusion: The authors concluded that future treatment of MPM may consist of a combination of immuno-oncology drugs or specific pathway inhibitors
• Limitations the authors state:
  • The authors note that the low incidence of mesothelioma has hampered larger randomized studies
  • The authors note that patients in studies are selected, so survival in trials may not reflect the general patient population

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, Pleural Mesothelioma.

Related studies

• Randomized comparison of cyclophosphamide, imidazole carboxamide, and adriamycin versus cyclophosphamide and adriamycin in patients with advanced stage malignant mesothelioma: a Sarcoma Intergroup Study — M.K. Samson, L.P. Wasser, et al. (1987)
• Priming the tumor immune microenvironment with chemo(radio)therapy: A systematic review across tumor types — T. van den Ende, H.G. van den Boorn, et al. (2020)
• Advances in systemic therapy for malignant mesothelioma: future perspectives — N. Sobhani, S.P. Corona, et al. (2017)
• Extended Pleurectomy-Decortication-Based Treatment for Advanced Stage Epithelial Mesothelioma Yielding a Median Survival of Nearly Three Years — J.S. Friedberg, C.B. Simone, et al. (2017)
• Long-term survival after lung-sparing total pleurectomy for locally advanced (International Mesothelioma Interest Group Stage T3-T4) non-sarcomatoid malignant pleural mesothelioma — A. Nakas, E. von Meyenfeldt, et al. (2012)
• Targeted next-generation sequencing of cancer genes in advanced stage malignant pleural mesothelioma: a retrospective study — M. Lo Iacono, V. Monica, et al. (2015)

Browse more research in Current Treatment Options in Oncology, or return to medical research.