Targeted therapies in malignant pleural mesothelioma: a review of clinical studies

Our plain-English summary of Targeted therapies in malignant pleural mesothelioma: a review of clinical studies, by L. Greillier, S. Marco, F. Barlesi (Anti-cancer Drugs, 2011).

The study

• Authors: L. Greillier, S. Marco, F. Barlesi
• Journal: Anti-cancer Drugs
• Published: 2011;22(3):199-205
• Type of article: Review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, whose exposure to asbestos fibers is the main etiology. The incidence of MPM is anticipated to increase worldwide during the first half of this century. MPM is notoriously refractory to most treatments, and the only standard of care is cisplatin and antifolate first-line chemotherapy. The urgent need for additional therapeutic agents, in parallel with advances in the knowledge of the molecular events of oncogenesis, has resulted in the development of the so-called 'targeted agents' that specifically inhibit critical pathways in malignant cells and in their microenvironment. We carried out a comprehensive review of the literature from January 2000 to May 2010 on studies that assessed targeted agents for the systemic treatment of MPM. Although tyrosine kinase inhibitors directed against the epidermal growth factor and the platelet-derived growth factor receptors did not show significant clinical activity in phase II studies, some other targeted therapies seemed promising, notably histone deacetylase inhibitors and antiangiogenic agents. However, none of these has yet reached daily practice. That is the reason why efforts must continue in the area of clinical and translational research for MPM.

In plain English

This article was a review, not a new study. The authors searched PubMed for clinical trials from January 2000 to May 2010 on 'targeted' drugs for malignant pleural mesothelioma. They also searched recent meeting abstracts and a registry of ongoing trials. They kept 11 clinical trials and 12 meeting communications. Asbestos exposure itself was not studied. In the phase II trials reviewed, drugs that block the epidermal growth factor and platelet-derived growth factor receptors, such as gefitinib, erlotinib and imatinib, failed to show significant clinical activity. The authors judged that histone deacetylase inhibitors might be a relevant strategy, with phase III results awaited. They also judged that antiangiogenic drugs, which target blood-vessel growth, seemed promising. Bevacizumab was the most advanced of these, with a phase III trial under way, and sorafenib showed activity in phase II studies. In early results from one ongoing trial, 57.4% of patients given bevacizumab with cisplatin and pemetrexed had their disease controlled, compared with 45.7% given the chemotherapy alone, among 93 patients assessable at 6 months. The authors concluded that none of these drugs had yet reached daily practice and that research must continue.

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: Literature review of clinical studies of targeted drug therapies
• Who was studied: Published clinical trials found in PubMed from January 2000 to May 2010, plus abstracts from international meetings (2006 to 2010) and ongoing trials listed on clinicaltrials.gov; 135 articles identified, of which 11 clinical trials were kept, plus 12 meeting communications
• Exposure: Not an asbestos exposure study. The 'exposure' reviewed was treatment of malignant pleural mesothelioma with targeted drugs (growth factor receptor inhibitors, histone deacetylase inhibitors, ranpirnase, antiangiogenic agents, proteasome inhibitors). The introduction describes asbestos fibers as the main cause of the disease.
• Main results:
  • The search kept 11 clinical trials, plus 12 communications from recent meetings
  • In the reviewed phase II trials, tyrosine kinase inhibitors directed against the EGF and PDGF receptors failed to show significant clinical activity
  • In the reviewed single-agent phase II trials of imatinib, there were no objective responses
  • The authors judged histone deacetylase inhibitors might be a relevant strategy; phase III results were awaited
  • Preliminary results of one ongoing randomized trial (cisplatin and pemetrexed with or without bevacizumab): among 93 patients assessable at 6 months, disease control was 57.4% in the bevacizumab arm and 45.7% in the control arm
  • Bevacizumab was the most advanced antiangiogenic agent in development, with an ongoing first-line phase III trial
  • Some multitargeted tyrosine kinase inhibitors with anti-VEGF activity, notably sorafenib, showed clinical activity in phase II studies
• The authors' conclusion: The authors concluded that some targeted therapies, notably HDAC inhibitors and antiangiogenic agents, seemed promising, but none had yet reached daily practice, and that research efforts must continue
• Limitations the authors state:
  • The authors noted that no imaging technique or biological marker had been validated to predict outcome in mesothelioma, which complicates judging the reviewed drugs
  • The authors noted that response criteria have always been difficult to apply to mesothelioma because of its growth pattern

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, Prognosis, Etiology, Cisplatin, Antifolate, Chemotherapy, Oncogenesis, Tyrosine Kinase Inhibitor.

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• Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy? — D. Signorelli, M. Macerelli, et al. (2016)
• Novel therapies for malignant pleural mesothelioma — A. Scherpereel, F. Wallyn, et al. (2018)
• Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma — R.E. Favoni, T. Florio (2011)
• Anti-angiogenic therapies for malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali (2012)
• Chemotherapy and targeted therapies for unresectable malignant mesothelioma — R.J. Kelly, E. Sharon, et al. (2011)

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