Closing faucets: the role of anti-angiogenic therapies in malignant pleural diseases

Our plain-English summary of Closing faucets: the role of anti-angiogenic therapies in malignant pleural diseases, by D. Marquez-Medina, S. Popat (Clinical & Translational Oncology, 2016).

The study

• Authors: D. Marquez-Medina, S. Popat
• Journal: Clinical & Translational Oncology
• Published: 2016;18(8):760-8
• Type of article: Review
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural effusion (MPE) represents 15-35 % of pleural effusions and markedly worsens the prognosis and quality of life of patients with cancer. Malignant mesothelioma (MM) and lung adenocarcinoma are the most frequent primary and secondary causes, respectively, of MPE. Effective treatments for cancer-related MPE are warranted in order to improve symptoms, reduce the number of invasive pleural procedures, and prolong patient life. Since angiogenesis plays a key role in MPE development, the potential role of bevacizumab and other anti-angiogenic therapies have been explored in this review. No relevant phase III trials have specifically analysed the benefit from adding bevacizumab to platinum-based chemotherapy in lung cancer-related MPE. However, small retrospective series reported 71.4-93.3 % MPE control rate, a reduction in invasive procedures, and a safe profile with this combination. Being approved for the first-line treatment of non-squamous advanced NSCLC, the addition of bevacizumab should be considered for patients presenting with MPE. In addition, further studies in this are recommended. In MM, the addition of bevacizumab to platinum-based chemotherapy did not meet primary endpoints in two phase II trials. However, the beneficial results on OS reported in comparison with historical cohorts and the statistically significant benefit on PFS and OS observed in the phase III MAPS trial foretell an eventual role for the combination of platinum/pemetrexed/bevacizumab as front-line systemic therapy for pleural MM. To date, no other anti-angiogenic drug has showed significant benefit in the treatment of patients with either MPE or MM. However, new promising drugs such as ramucirumab or recombinant human endostar warrant further investigation.

In plain English

This article was a review, not a new study. The authors reviewed published research on drugs that block blood-vessel growth (anti-angiogenic therapies), mainly bevacizumab. They looked at two conditions: malignant pleural effusion (fluid around the lungs that contains cancer cells) and malignant mesothelioma. For effusions caused by lung cancer, the authors reported that no relevant phase III trial had specifically tested adding bevacizumab to platinum-based chemotherapy. Small retrospective series reported effusion control rates of 71.4 to 93.3 percent. In mesothelioma, adding bevacizumab did not meet the primary goals of two phase II trials. In one placebo-controlled phase II trial of 108 patients, differences in response, progression-free survival and overall survival were not statistically significant. In the phase III MAPS trial of 448 patients with unresectable pleural mesothelioma, adding bevacizumab to cisplatin and pemetrexed was reported to lengthen median progression-free survival (9.6 vs. 7.5 months) and overall survival (18.8 vs. 16 months). The authors found that no other anti-angiogenic drug had obtained significant clinical results. They concluded that the bevacizumab combination should be considered for patients with advanced non-squamous non-small cell lung cancer who have malignant pleural effusion, since it is already approved as first-line treatment for that cancer. They also said further study is warranted.

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 studies
• Who was studied: No participants of its own. It reviewed published studies, case reports and animal experiments on patients with malignant pleural effusion (mainly from non-small cell lung cancer) and with malignant mesothelioma.
• Exposure: Anti-angiogenic drug treatments, mainly bevacizumab combined with chemotherapy, and also tyrosine kinase inhibitors, thalidomide, interferon and endostar. Asbestos exposure was not studied.
• Main results:
  • For lung cancer-related malignant pleural effusion, the reviewed small retrospective series reported effusion control rates of 71.4 to 93.3 percent with chemotherapy plus bevacizumab.
  • In a reviewed randomized double-blind phase II trial of 108 patients with unresectable mesothelioma, adding bevacizumab to cisplatin/gemcitabine did not significantly increase overall response rate (24.5 vs. 21.8 %; p = 0.74), progression-free survival (6.9 vs. 6 months; p = 0.62) or overall survival (15.6 vs. 14.7 months; p = 0.91).
  • In the reviewed phase III MAPS trial (448 randomized patients with unresectable pleural mesothelioma), bevacizumab added to cisplatin/pemetrexed increased median progression-free survival (9.6 vs. 7.5 months; p less than 0.0001).
  • In the MAPS trial, median overall survival was 18.8 vs. 16 months (p = 0.012) with bevacizumab vs. without, with no differences in quality of life.
  • The authors reported that, to date, no anti-angiogenic drug other than bevacizumab had obtained significant clinical results in these diseases.
• The authors' conclusion: The authors concluded that chemotherapy plus bevacizumab should be considered for patients presenting with malignant pleural effusion, as it is already approved for first-line treatment of advanced non-squamous non-small cell lung cancer, and that further evaluation is warranted. In mesothelioma, they concluded that the MAPS trial and the comparisons with historical groups point to a role for platinum/pemetrexed/bevacizumab.
• Limitations the authors state:
  • The authors stated that no relevant prospective phase III trial had specifically analysed adding bevacizumab in lung cancer-related malignant pleural effusion. The supporting data came from small retrospective series.
  • The authors noted that the favorable survival results in the phase II mesothelioma trials came from comparison with historical groups, while the trials themselves did not reach their primary endpoints.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Prognosis, Quality of Life, Mesothelioma, Lung Adenocarcinoma, Angiogenesis, Bevacizumab, Chemotherapy.

Related studies

• Anti-angiogenic therapies for malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali (2012)
• Current data on predictive markers for anti-angiogenic therapy in thoracic tumours — N. Reinmuth, M. Thomas, et al. (2010)
• 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)
• Recombinant human endostatin (endostar) decreased recurrent ascites, pleural fluid and ascitic VEGF in a case of advanced mesothelioma — X. Chen, Y. Liu, et al. (2012)
• Novel therapies for malignant pleural mesothelioma — A. Scherpereel, F. Wallyn, et al. (2018)

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