Chemotherapy and targeted therapies for unresectable malignant mesothelioma

Our plain-English summary of Chemotherapy and targeted therapies for unresectable malignant mesothelioma, by R.J. Kelly, E. Sharon, R. Hassan (Lung Cancer, 2011).

The study

• Authors: R.J. Kelly, E. Sharon, R. Hassan
• Journal: Lung Cancer
• Published: 2011;73(3):256-63
• Type of article: Review
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The global burden of mesothelioma is expected to increase in the coming decades. As a result the development of more effective therapies with an emphasis on personalized treatments based on validated prognostic and predictive biomarkers is an essential requirement. Progress has been made in the last decade with the development of newer generation anti-folates leading to the current standard of care of pemetrexed and cisplatin in patients with unresectable disease. However, the median overall survival of patients with this combination treatment is only 12 months. There is no consensus regarding second line therapy for patients who have progressed or not responded to pemetrexed based therapies although gemcitabine in combination with a platinum compound or single agent vinorelbine is a reasonable option. The development of effective targeted agents that are active in mesothelioma has to date been disappointing. Strategies involving the addition of bevacizumab to pemetrexed and cisplatin in the frontline setting, the histone deacetylase inhibitor vorinostat as second line therapy and studies evaluating the utility of maintenance therapy in mesothelioma are all ongoing and appear promising. In addition clinical trials investigating immunotherapy and gene therapy in combination with chemotherapy could potentially improve the prognosis of patients with mesothelioma.

Published by Elsevier Ireland Ltd.

In plain English

This article was a review of drug treatments for malignant mesothelioma that cannot be removed by surgery. It reported no new patient data of its own. The authors summarized published and ongoing trials of chemotherapy, targeted drugs, immunotherapy and gene therapy, mostly in malignant pleural mesothelioma. In one Phase III trial of 456 patients that they described, cisplatin plus pemetrexed gave a median overall survival of 12.1 months, compared with 9.3 months for cisplatin alone. The authors stated that this combination remains the standard of care. A large access program reported similar one-year survival when pemetrexed was given with carboplatin (64.0%) or with cisplatin (63.1%). For second-line treatment, the authors considered single-agent vinorelbine a reasonable option. The targeted-drug trials they reviewed, such as those of EGFR inhibitors, showed little activity. In a trial that added bevacizumab to cisplatin and gemcitabine, the main endpoint did not reach statistical significance. The review did not study asbestos exposure. It mentioned asbestos only as background on the cause of the disease.

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 and ongoing clinical trials; no new data collected
• Who was studied: Patients with unresectable malignant mesothelioma, mostly malignant pleural mesothelioma (MPM), as enrolled in the trials reviewed; the review itself had no study population
• Exposure: Not studied. The review concerns drug treatments (chemotherapy, targeted agents, immunotherapy, gene therapy). Asbestos is mentioned only in the introduction as background on the cause of mesothelioma.
• Main results:
  • In the Phase III trial by Vogelzang et al. (456 chemotherapy-naive patients not eligible for curative surgery), median overall survival was 12.1 months with pemetrexed plus cisplatin vs. 9.3 months with cisplatin alone (P = .020)
  • In the EORTC Phase III trial (250 treatment-naive patients), median overall survival was 11.4 months with cisplatin plus raltitrexed vs. 8.8 months with cisplatin alone (P = .048)
  • In the nonrandomized International Expanded Access Program, 1-year survival was 63.1% with pemetrexed plus cisplatin (n = 843) vs. 64.0% with pemetrexed plus carboplatin (n = 861)
  • In a second-line trial of 63 patients with relapsed pleural mesothelioma, weekly single-agent vinorelbine had a response rate of 16% and an overall survival of 9.6 months; the authors considered it reasonable second-line treatment for pleural mesothelioma
  • In the MS01 trial, adding chemotherapy to active symptom control did not improve overall survival
  • In a Phase II trial of gefitinib in 43 previously treated patients, one partial and one complete response were observed; the authors described EGFR inhibitor results as disappointing
  • In a randomized Phase II trial of cisplatin and gemcitabine with or without bevacizumab, progression-free survival was 6.9 months (bevacizumab arm) vs. 6.0 months (placebo arm), which did not reach statistical significance
• The authors' conclusion: The authors concluded that cisplatin plus pemetrexed remains the standard chemotherapy, that targeted therapies such as EGFR and VEGF inhibitors have so far had limited activity, and that results of ongoing trials are awaited
• Limitations the authors state:
  • The authors noted that findings linking low thymidylate synthase (TS) expression to better outcomes came from retrospective studies and need confirmation in a prospective trial before routine use
  • The authors noted that the MS01 trial did not reach its planned size because of slow accrual, and that the apparent vinorelbine survival benefit came from an exploratory analysis and was not statistically significant

Topics

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

Medical terms in this study, explained in our Lexicon: Chemotherapy, Unresectable, Malignant Mesothelioma, Mesothelioma, Biomarker, Pemetrexed (Alimta), Cisplatin, Median Overall Survival.

Related studies

• Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma — R.E. Favoni, T. Florio (2011)
• Successful salvage chemotherapy with gemcitabine and vinorelbine in a malignant pleural mesothelioma patient previously treated with pemetrexed — T. Agatsuma, T. Koizumi, et al. (2010)
• Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy? — D. Signorelli, M. Macerelli, et al. (2016)
• Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms — Z.G. Fridlender, J. Sun, et al. (2010)
• Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy — G. Toyokawa, M. Takenoyama, et al. (2014)
• PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy — B.K. Bitanihirwe, M. Meerang, et al. (2014)

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