A review of bevacizumab in the treatment of malignant pleural mesothelioma

Our plain-English summary of A review of bevacizumab in the treatment of malignant pleural mesothelioma, by S. Brosseau, S. Assoun, C. Naltet, et al (Future Oncology, 2017).

The study

• Authors: S. Brosseau, S. Assoun, C. Naltet, C. Steinmetz, V. Gounant, G. Zalcman
• Journal: Future Oncology
• Published: 2017;13(28):2537-2546
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. Systemic chemotherapy is the primary treatment modality for the majority of patients. VEGF plays a key mitogen for MPM cells physiopathology. Bevacizumab, a monoclonal anti-VEGF antibody, was a rational approach to be tested in MPM. Based on the results of the Phase III IFCT-0701 mesothelioma avastin cisplatin pemetrexed study, cisplatin-pemetrexed-bevacizumab is now the accepted standard in France. The National Comprehensive Cancer Network guidelines have also included this combination as an option for standard front-line therapy. This review summarized the efficacy and safety data of bevacizumab in the treatment of patients with MPM.

In plain English

This article is a review, not a new study. The authors reviewed published clinical trials of bevacizumab, a drug that blocks a growth signal called VEGF, in patients with malignant pleural mesothelioma. Asbestos is mentioned only as background. In the largest trial reviewed, the MAPS trial of 448 patients, adding bevacizumab to pemetrexed-cisplatin chemotherapy was reported to lengthen median progression-free survival (9.2 vs 7.3 months) and median overall survival (18.8 vs 16.1 months). The bevacizumab group had more grade 3 high blood pressure and more patients stopping treatment because of side effects. In one earlier randomized trial reviewed, of 108 patients with pleural or peritoneal mesothelioma, adding bevacizumab to a different chemotherapy did not significantly improve survival. Most other drugs of this type that were reviewed failed to show benefit. The authors concluded that bevacizumab with cisplatin and pemetrexed should be considered the new standard for suitable patients younger than 76 who are not candidates for radical surgery. They noted that the trials found no marker showing who benefits most, and that MAPS included only patients younger than 76.

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 literature review (drug evaluation) of published clinical trials of bevacizumab in malignant pleural mesothelioma
• Who was studied: Patients in the published trials reviewed. The largest was the Phase II/III MAPS trial, with 448 eligible patients with malignant pleural mesothelioma randomized to cisplatin/pemetrexed with or without bevacizumab. Smaller Phase II trials had 24, 108 (pleural or peritoneal mesothelioma), 76 and 53 patients.
• Exposure: No asbestos exposure was studied. Occupational inhalation of asbestos is named only in the background as the main cause of malignant pleural mesothelioma. The treatment reviewed was bevacizumab, given alone or combined with chemotherapy or erlotinib.
• Main results:
  • MAPS trial, bevacizumab group compared with chemotherapy alone: median progression-free survival 9.2 vs 7.3 months (adjusted HR = 0.61; p less than 0.0001) and median overall survival 18.8 vs 16.1 months (adjusted HR = 0.75; p = 0.0167), as given in the text
  • MAPS trial: grade 3 hypertension in 22% of the bevacizumab arm vs 0% of the control arm
  • MAPS trial: more patients in the bevacizumab arm stopped treatment because of toxicity (24.3% vs 13%)
  • Kindler randomized Phase II trial (108 patients with pleural or peritoneal mesothelioma): adding bevacizumab to gemcitabine/cisplatin did not significantly improve progression-free survival (6.9 vs 6 months, p = 0.88) or overall survival (15.6 vs 14.7 months, p = 0.91)
  • Ceresoli single-arm Phase II trial (76 patients, bevacizumab with carboplatin/pemetrexed): median progression-free survival 6.9 months and overall survival 15.3 months. The trial did not reach its primary end point.
  • Jackman Phase II trial of bevacizumab with erlotinib in previously treated patients: no complete or partial responses. 12 of 24 patients had stable disease for at least two cycles.
  • Other antiangiogenic drugs reviewed failed to show efficacy, except nintedanib in a randomized Phase II trial that had yet to be confirmed in Phase III
• The authors' conclusion: The authors concluded that bevacizumab plus cisplatin and pemetrexed should be considered the new standard regimen for patients with malignant pleural mesothelioma aged under 76 who are eligible for bevacizumab and not candidates for radical surgery, whatever the histology
• Limitations the authors state:
  • The published trials failed to identify biomarkers showing which patients benefit most from bevacizumab
  • MAPS included only patients younger than 76, and a higher risk of bleeding has been reported in older patients
  • The authors described the Kindler Phase II trial as probably underpowered

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: Bevacizumab, Pleural Mesothelioma, Prognosis, Chemotherapy, Monoclonal Antibody, Mesothelioma, Cisplatin, Pemetrexed (Alimta).

Related studies

• Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma: A Case Report and Literatures Review — X.Q. Jing, L. Zhou, et al. (2016)
• Novel therapies for malignant pleural mesothelioma — A. Scherpereel, F. Wallyn, et al. (2018)
• Anti-angiogenic therapies for malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali (2012)
• Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial — C. Pinto, P.A. Zucali, et al. (2021)
• Targeted therapies in malignant pleural mesothelioma: a review of clinical studies — L. Greillier, S. Marco, et al. (2011)
• A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma — J.E. Dowell, F.R. Dunphy, et al. (2012)

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