Anti-angiogenic therapies for malignant pleural mesothelioma

Our plain-English summary of Anti-angiogenic therapies for malignant pleural mesothelioma, by G.L. Ceresoli, P.A. Zucali (Expert Opinion on Investigational Drugs, 2012).

The study

• Authors: G.L. Ceresoli, P.A. Zucali
• Journal: Expert Opinion on Investigational Drugs
• Published: 2012;21(6):833-44
• Type of article: Review
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is a disease with a dismal prognosis. Currently available treatments have modest results. Therefore, new agents and new treatment strategies are eagerly awaited by patients and clinicians. Preclinical and clinical studies have shown that angiogenesis plays a very important role in MPM. Therefore, a great hope has been placed in the use of anti-angiogenic agents in this disease.

Areas Covered: Studies regarding anti-angiogenic treatments in MPM with bevacizumab, tyrosine-kinase inhibitors (TKIs) and other agents were critically analyzed, with an overview of ongoing trials and future perspectives, including research on biomarkers.

Expert Opinion: The clinical use of angiogenesis inhibitors in MPM patients has resulted more challenging than anticipated. The intrinsic complexity of neo-angiogenesis, and its redundant regulatory mechanisms, suggests that multiple and different biomarkers are needed to predict efficacy of anti-angiogenic agents and to monitor their biological and therapeutic effects. The growing understanding of the molecular alterations and key pathways that underlie the resistance to VEGF inhibitors will allow to design studies of the combination of agents targeting these pathways with anti-VEGF therapies. Only a tight integration of preclinical and clinical studies will allow to achieve a real progress in MPM patients with this therapeutic strategy.

In plain English

This article was a review, not a new study. The authors searched PubMed, Cancerlit, conference abstracts and the clinicaltrials.gov website for published and ongoing trials of drugs that block blood-vessel growth (anti-angiogenic drugs) in malignant pleural mesothelioma. They also reviewed research on markers that might predict who benefits. In the only randomized bevacizumab trial with available results, adding bevacizumab to cisplatin and gemcitabine did not produce statistically significant differences in progression-free survival (6.9 vs 6.0 months) or overall survival (15.6 vs 14.7 months). In a randomized phase III trial of 222 patients, maintenance thalidomide showed no evidence of benefit. The authors described single-drug trials of tyrosine-kinase inhibitors, mostly given after earlier chemotherapy, as having similar, disappointing results. They noted that validated biomarkers were still lacking and that nearly all available studies had important limitations, including small and mixed patient groups. The authors concluded that these drugs had proved more challenging than anticipated. They added that real progress would require tight integration of laboratory and clinical research.

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 literature, conference abstracts and ongoing trials
• Who was studied: Published studies and ongoing trials of anti-angiogenic treatment in malignant pleural mesothelioma patients. Sources were PubMed, Cancerlit, abstracts from ASCO, ESMO, IASLC and IMIG meetings, and clinicaltrials.gov. No new patients were studied.
• Exposure: No asbestos exposure was studied. The review covered anti-angiogenic drug treatments: bevacizumab, thalidomide, multi-targeted tyrosine-kinase inhibitors (for example sorafenib, sunitinib, vatalanib, cediranib) and other agents such as NGR-hTNF.
• Main results:
  • In a reviewed randomized phase II trial (115 enrolled, 108 evaluable), adding bevacizumab to cisplatin-gemcitabine gave no statistically significant difference. Progression-free survival was 6.9 vs 6.0 months (HR 0.93, p = 0.88) and overall survival 15.6 vs 14.7 months (HR 1.13, p = 0.91).
  • In a subgroup analysis of that same trial, patients with VEGF levels below the median had longer progression-free and overall survival with bevacizumab. Another reviewed phase II study found no difference by baseline VEGF levels.
  • In a reviewed randomized phase III maintenance trial (222 patients), median progression-free survival was 16 weeks with thalidomide vs 15 weeks with observation (p = 0.83, HR 1.0). Median overall survival was 11 vs 13 months (p = 0.09, HR 0.78).
  • The authors summarized single-agent tyrosine-kinase inhibitor trials, mostly given after earlier treatment, as showing similar, disappointing results.
  • In four reviewed phase II trials, imatinib mesylate produced no responses in either untreated or previously treated patients.
  • The authors found that validated biomarkers to predict response or identify resistant patients were still lacking.
• The authors' conclusion: The authors concluded that clinical use of angiogenesis inhibitors in malignant pleural mesothelioma had been more challenging than anticipated, and that real progress would require tight integration of preclinical and clinical studies.
• Limitations the authors state:
  • The authors stated that nearly all available studies had important limitations: small numbers of patients, mixed (heterogeneous) patient groups, and often the study design.
  • The authors cautioned that comparing single-arm bevacizumab trials with historical controls is indirect, because patient selection and trial designs differed.

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, Angiogenesis, Bevacizumab, Biomarker, VEGF inhibitors.

Related studies

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• Closing faucets: the role of anti-angiogenic therapies in malignant pleural diseases — D. Marquez-Medina, S. Popat (2016)
• Targeting the vasculature: anti-angiogenic agents for malignant mesothelioma — P.L. Chia, P.A. Russell, et al. (2016)
• Combinatorial anti-angiogenic gene therapy in a human malignant mesothelioma model — S. Kubo, M. Takagi-Kimura, et al. (2015)
• Targeted therapies in malignant pleural mesothelioma: a review of clinical studies — L. Greillier, S. Marco, et al. (2011)
• Translational therapies for malignant pleural mesothelioma — C. Belli, S. Anand, et al. (2010)

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