Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy?

Our plain-English summary of Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy?, by D. Signorelli, M. Macerelli, C. Proto, et al (Tumori, 2016).

The study

• Authors: D. Signorelli, M. Macerelli, C. Proto, M. Vitali, M.S. Cona, F. Agustoni, N. Zilembo, M. Platania, A. Trama, R. Gallucci, M. Ganzinelli, G. Pelosi, U. Pastorino, F. de Braud, M.C. Garassino, G. Lo Russo
• Journal: Tumori
• Published: 2016;102(1):18-30
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is a rare cancer with a cause-effect relationship to asbestos exposure. The prognosis is poor and chemotherapy seems the best treatment option. In the last two decades a deeper understanding of mesothelioma carcinogenesis and invasiveness mechanisms has prompted research efforts to test new agents in patients with malignant pleural mesothelioma, but the results have been modest. Attractive preclinical data disappointed in subsequent experimental phases. Other promising agents failed to improve patient outcomes due to high toxicity. Interesting suggestions have come from preliminary data on immunotherapy. Several trials are ongoing and the results are eagerly awaited. The aim of this review is to discuss the most recent news on systemic therapy for advanced malignant pleural mesothelioma.

In plain English

This article is a review of clinical trials of drug treatment for advanced malignant pleural mesothelioma (MPM): chemotherapy, targeted drugs and immunotherapy. It did not study new patients and did not study asbestos exposure. Its background section describes asbestos as the main risk factor. Describing earlier trials, the review reported that in a phase III study of 456 patients, median survival was 12.1 months with cisplatin plus pemetrexed versus 9.3 months with cisplatin alone. Preliminary data from the French MAPS trial showed median overall survival of 18.8 versus 16.1 months in favor of adding bevacizumab. A phase III trial of vorinostat in 661 patients reported median survival of 30.7 weeks versus 27.1 weeks on placebo, failing its primary endpoint. Thalidomide maintenance showed no benefit over best supportive care. In a phase II trial of the immunotherapy drug tremelimumab in 29 patients, 31% achieved disease control. The authors concluded that targeted drugs used alone failed to show significant activity in unselected patients or had unacceptable toxicity. They also concluded that immunotherapy could be safer, but that it is too early to consider it effective.

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 clinical trials of systemic (drug) therapy for advanced malignant pleural mesothelioma
• Who was studied: No new patients. The review covered published and ongoing clinical trials in patients with advanced malignant pleural mesothelioma, summarized in tables by drug class.
• Exposure: No exposure was studied; the review concerns treatments (chemotherapy, targeted agents, immunotherapy). Its background section describes asbestos as the main risk factor for MPM.
• Main results:
  • In a reviewed phase III trial (Vogelzang et al, 456 chemotherapy-naive patients), median survival was 12.1 months in the cisplatin plus pemetrexed arm versus 9.3 months in the cisplatin-alone arm (hazard ratio for death 0.77).
  • Preliminary data from the reviewed French phase III MAPS trial showed median overall survival of 18.8 months versus 16.1 months (HR 0.76, 95% CI 0.61-0.94, p = 0.012) in favor of adding bevacizumab to cisplatin and pemetrexed.
  • In a reviewed phase III trial of vorinostat in 661 previously treated patients, the primary endpoint (overall survival) was not met: median 30.7 weeks for vorinostat versus 27.1 weeks for placebo (HR 0.98, 95% CI 0.83-1.17, p = 0.86).
  • In a reviewed phase III trial, thalidomide maintenance after platinum plus pemetrexed showed no benefit compared with best supportive care (time to progression 3.6 vs 3.5 months, p = 0.72).
  • In a reviewed phase II trial of the immunotherapy drug tremelimumab in 29 previously treated patients, the primary endpoint (objective response rate) was not reached. However, 31% of patients achieved disease control (2 partial responses and 7 stable disease), all with epithelioid histology.
  • In the authors' overall assessment, targeted agents used as single drugs failed to show significant activity in unselected patients or were associated with unacceptable toxicity.
• The authors' conclusion: The authors concluded that MPM prognosis remains poor and new drugs are needed. They concluded that immunotherapy could be a safer approach, but that it is too early to consider it effective.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Chemotherapy, Immunotherapy, Asbestos Exposure, Prognosis, Mesothelioma, Carcinogenesis, Systemic Therapy.

Related studies

• Targeted therapies in malignant pleural mesothelioma: a review of clinical studies — L. Greillier, S. Marco, et al. (2011)
• Chemotherapy and targeted therapies for unresectable malignant mesothelioma — R.J. Kelly, E. Sharon, et al. (2011)
• Mesothelin Immunotherapy for Cancer: Ready for Prime Time? — R. Hassan, A. Thomas, et al. (2016)
• Novel targeted therapies and vaccination strategies for mesothelioma — M. Bagia, A.K. Nowak (2011)
• Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma — R.E. Favoni, T. Florio (2011)
• Is there a role for immunotherapy in malignant pleural mesothelioma? — A. Tartarone, R. Lerose, et al. (2018)

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