New horizons from novel therapies in malignant pleural mesothelioma

Our plain-English summary of New horizons from novel therapies in malignant pleural mesothelioma, by M. Sayan, S. Mamidanna, M. Fuat Eren, et al (Advances in Respiratory Medicine, 2020).

The study

• Authors: M. Sayan, S. Mamidanna, M. Fuat Eren, V. Daliparty, T. Zoto Mustafayev, C. Nelson, N. Ohri, S.K. Jabbour, A. Guven Mert, B. Atalar
• Journal: Advances in Respiratory Medicine
• Published: 2020;88(4):343-351
• Type of article: Review
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.

In plain English

This article is a review, not a new study. The authors reviewed published research on treating malignant pleural mesothelioma (MPM), a cancer of the lining around the lungs, which they attributed to prolonged exposure to airborne asbestos particles. They described the standard treatment, which combines surgery with chemotherapy and/or radiotherapy. They also reviewed laboratory, animal and clinical research on cell survival pathways (EGFR, ERK, CREB and AKT) that may help tumor cells resist radiation and chemotherapy, and on immunotherapy. In the earlier studies they cited, median survival with MPM was estimated at 8 to 14 months, and early gefitinib trials showed no clinical efficacy. In the cited DETERMINE trial of 571 patients, tremelimumab did not significantly prolong survival. Other cited trials reported a 20% response rate among 25 patients given pembrolizumab, and a 38% response rate among 36 patients given ipilimumab with nivolumab, where 94% reported an adverse event. The authors concluded that drugs targeting these pathways, combined with radiotherapy, might help overcome radiation resistance. They called for further research and clinical trials. The review reported no new data of its own.

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 laboratory, animal and clinical studies on MPM treatment
• Who was studied: No study population of its own; the authors reviewed published studies of MPM treatment (cell lines, animal models and clinical trials)
• Exposure: Not an exposure study; asbestos is mentioned only as the cause of MPM, with no fiber types named. The review covers treatments: surgery, radiotherapy, chemotherapy, targeted inhibitors and immunotherapy.
• Main results:
  • Cited from other research: median survival of patients with MPM estimated at 8 to 14 months
  • Cited from other research: early clinical trials of gefitinib showed no clinical efficacy in MPM patients
  • Cited from other research: PD-L1 positive MPM was associated with poorer prognosis than PD-L1 negative MPM (median survival 4.8 to 5.0 months vs 14.5 to 16.3 months)
  • Cited KEYNOTE-028 phase I trial: among 25 patients given pembrolizumab, disease control rate was 72% and response rate 20%
  • Cited DETERMINE randomized trial (571 patients): tremelimumab did not significantly prolong survival or improve response compared with placebo in previously treated patients
  • Cited MAPS-II trial (125 patients with relapsed MPM): drug-related adverse events were 93% with nivolumab plus ipilimumab vs 89% with nivolumab alone
  • Cited INITIATE trial (36 eligible patients with recurrent MPM, ipilimumab with nivolumab): response rate 38%, disease control rate 68%, and 94% reported an adverse event
• The authors' conclusion: The authors concluded that inhibitors targeting the EGFR, ERK, CREB and AKT pathways, combined with radiotherapy, might help overcome tumor radiation resistance, and that more research and clinical trials are needed.
• Limitations the authors state:
  • The authors note that the lack of randomized controlled trials means the best surgical procedure cannot yet be determined

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelial Cells, Asbestos Exposure, Trimodality Therapy, Chemotherapy, Damages, Mesothelioma.

Related studies

• Malignant pleural mesothelioma: new hope in the horizon with novel therapeutic strategies — J. Remon, N. Reguart, et al. (2015)
• Novel induction therapies for pleural mesothelioma — L. Donahoe, J. Cho, et al. (2014)
• Novel targeted therapies and vaccination strategies for mesothelioma — M. Bagia, A.K. Nowak (2011)
• Novel therapies for malignant pleural mesothelioma — A. Scherpereel, F. Wallyn, et al. (2018)
• Novel intrapleural therapies for malignant diseases — A.R. Haas, D.H. Sterman (2012)
• Chemotherapy and targeted therapies for unresectable malignant mesothelioma — R.J. Kelly, E. Sharon, et al. (2011)

Browse return to medical research.