Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma

Our plain-English summary of Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma, by A. Tsao, T. Nakano, A.K. Nowak, et al (Seminars in Oncology, 2019).

The study

• Authors: A. Tsao, T. Nakano, A.K. Nowak, S. Popat, G.V. Scagliotti, J. Heymach
• Journal: Seminars in Oncology
• Published: 2019;46(2):145-154
• Type of article: Review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a global health issue, the principal cause of which is exposure to asbestos. The prevalence is anticipated to rise over the next 2 decades, particularly in developing countries, due to the 30-50-year latency period between exposure to asbestos and carcinogenic development. Unresectable MPM has a poor prognosis and limited treatment options and, as such, there is a broad range of therapeutic targets of interest, including angiogenesis, immune checkpoints, mesothelin, as well as chemotherapeutic agents. Recently, the results of several randomized trials in the first-line setting combining antiangiogenic agents with chemotherapy have been reported. This review examines the scientific rationale for targeting angiogenesis in the treatment of unresectable MPM and analyzes recent clinical results with antiangiogenic agents in development (bevacizumab, nintedanib, and cediranib) for the management of MPM.

Copyright © 2019. Published by Elsevier Inc.

In plain English

This article is a review, not a new study. The authors examined why blocking angiogenesis (the growth of new blood vessels) might help treat malignant pleural mesothelioma that cannot be removed by surgery. They summarized trial results for such drugs, mainly bevacizumab, nintedanib and cediranib. They note that asbestos exposure is the principal cause of this cancer, but the review did not study exposure. In the MAPS trial of 448 patients, adding bevacizumab to cisplatin/pemetrexed chemotherapy gave a median overall survival of 18.8 months, against 16.1 months with chemotherapy alone. More patients stopped treatment because of side effects with bevacizumab (24.3% versus 6.0%). In the LUME-Meso trial, nintedanib improved progression-free survival in the phase II part (87 patients). The phase III part (458 patients) did not confirm this. In a phase II trial of 92 patients, the response rate measured by modified RECIST criteria was 53% with cediranib plus cisplatin/pemetrexed, against 20% with cisplatin/pemetrexed alone. Earlier single-drug trials were generally disappointing. The authors concluded that results were mixed and that more data are needed.

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 laboratory evidence and published clinical trials of antiangiogenic drugs in malignant pleural mesothelioma
• Who was studied: Patients with unresectable malignant pleural mesothelioma enrolled in the clinical trials the review summarizes; the review itself enrolled no patients
• Exposure: No asbestos exposure was studied. The review concerns drug treatments: antiangiogenic agents (bevacizumab, nintedanib, cediranib and others), usually added to cisplatin/pemetrexed chemotherapy. The authors state as background that asbestos exposure is the principal cause of malignant pleural mesothelioma.
• Main results:
  • MAPS trial (448 previously untreated patients with unresectable MPM, as reported in the review): adding bevacizumab to cisplatin/pemetrexed gave a median overall survival of 18.8 months, compared with 16.1 months for chemotherapy alone (HR 0.77, 95% CI 0.62 to 0.95; P = 0.0167).
  • MAPS trial: stopping treatment because of adverse events happened in 24.3% of patients in the bevacizumab arm and 6.0% of patients in the chemotherapy-alone arm.
  • LUME-Meso phase II (87 patients with nonsarcomatoid MPM): adding nintedanib to cisplatin/pemetrexed improved median progression-free survival compared with placebo (9.4 v 5.7 months; HR 0.54; 95% CI 0.33 to 0.87; P = 0.010). Overall survival showed a trend that was not significant (18.3 v 14.2 months; HR 0.77; 95% CI 0.46 to 1.29; P = 0.319).
  • LUME-Meso phase III (458 patients with epithelioid MPM): the primary endpoint was not met. Median progression-free survival was 6.8 months with nintedanib and 7.0 months with placebo (HR 1.01, 95% CI 0.79 to 1.30; P = 0.914). Interim median overall survival was 14.4 versus 16.1 months (HR 1.12, 95% CI 0.79 to 1.58; P = 0.538).
  • SWOG S0905 phase II (92 patients): cediranib plus cisplatin/pemetrexed improved modified RECIST response rates compared with cisplatin/pemetrexed alone (53% v 20%, P = 0.01). It showed a trend toward longer progression-free survival (median 7.2 v 5.6, HR 0.69, P = 0.096).
  • Earlier trials of antiangiogenic drugs used alone, mostly in relapsed disease, were generally disappointing: either they showed a lack of clinical benefit or the drugs were poorly tolerated.
• The authors' conclusion: The authors concluded that antiangiogenic therapy has yielded mixed results. They wrote that it has the potential to improve the outlook for patients with MPM, but that further data and identification of the patients who can benefit are needed.

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: Angiogenesis, Unresectable, Pleural Mesothelioma, Latency, Carcinogenic, Prognosis, Mesothelin, Chemotherapy.

Related studies

• LUME-Meso: Design and Rationale of the Phase III Part of a Placebo-Controlled Study of Nintedanib and Pemetrexed/Cisplatin Followed by Maintenance Nintedanib in Patients With Unresectable Malignant Pleural Mesothelioma — G.V. Scagliotti, R. Gaafar, et al. (2017)
• Phase I Trial of Cediranib in Combination with Cisplatin and Pemetrexed in Chemonaive Patients with Unresectable Malignant Pleural Mesothelioma (SWOG S0905) — A.S. Tsao, J. Moon, et al. (2017)
• VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours — Y. Ohta, V. Shridhar, et al. (1999)
• The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease — K.J. O'Byrne, A.G. Dalgleish, et al. (2000)
• Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma — J.G. Edwards, D.E. Swinson, et al. (2003)
• Induction of angiogenesis by intraperitoneal injection of asbestos fibers — R.M. Branchaud, J.L. MacDonald, et al. (1989)

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