Systemic treatment of malignant pleural mesothelioma: new agents in clinical trials raise hope of relevant improvements

Our plain-English summary of Systemic treatment of malignant pleural mesothelioma: new agents in clinical trials raise hope of relevant improvements, by D.C. Christoph, W.E. Eberhardt (Current Opinion in Oncology, 2014).

The study

• Authors: D.C. Christoph, W.E. Eberhardt
• Journal: Current Opinion in Oncology
• Published: 2014;26(2):171-81
• Type of article: Review
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose Of Review: Malignant pleural mesothelioma (MPM) is a rare malignancy with limited therapeutic options and its incidence is still increasing in both Europe and the developing nations. Prognosis of MPM patients is poor even if the median survival durations have been slightly improved after the introduction of the up-to-date chemotherapy combination with pemetrexed and cisplatin. There is a continuing unmet need to develop better systemic treatment for this disease, but the rarity of the tumor type creates formidable challenges in clinical trial research.

Recent Findings: Better understanding of the molecular machinery of MPM leads to the design and synthesis of novel compounds targeted against pathways identified as crucial for MPM cell proliferation and metastasis. Most efforts aim at improving standard first-line therapy, or developing effective second-line treatments. Several classes of drugs are currently being explored either in combination with cisplatin and pemetrexed or as single agent for relapsed or progressive MPM.

Summary: This review focuses on several ongoing or recently completed clinical trials investigating novel, promising agents as first-line or second-line therapy for advanced MPM.

In plain English

This article was a review. It did not study asbestos exposure; its introduction stated, citing earlier work, that asbestos fiber exposure is widely accepted as the main cause of malignant pleural mesothelioma (MPM). The authors described recent and ongoing trials of new drugs for unresectable and advanced MPM. These included drugs aimed at tumor blood vessels, such as bevacizumab and cediranib, and others such as tremelimumab and everolimus. Some results were preliminary. In the phase II part of a French trial, disease control at 6 months was 73.5% with bevacizumab plus chemotherapy versus 43.2% in controls. With cediranib plus chemotherapy, the response rate was 53% among 19 patients assessed by modified RECIST and 22% among 18 assessed by standard RECIST 1.1. With tremelimumab, 2 of 29 previously treated patients (7%) had a durable partial remission, though the trial did not meet its primary endpoint. Single-agent everolimus showed a lack of activity in unselected patients. The authors concluded that cediranib warranted further study, that bevacizumab phase III results were pending, and that more new agents were in trials than ever before.

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 recently completed and ongoing clinical trials of drug treatments
• Who was studied: Patients with advanced or unresectable malignant pleural mesothelioma enrolled in ongoing or recently completed clinical trials of first-line or second-line drug therapy, as reported in other publications. The review itself enrolled no patients.
• Exposure: Drug treatments, not asbestos. These were antiangiogenic and vascular disrupting agents (bevacizumab, sorafenib, sunitinib, vatalanib, axitinib, cediranib, BNC105P, NGR-hTNF-a) and other agents (bortezomib, ADI-PEG20, amatuximab, GC1008, tremelimumab, everolimus). Asbestos was mentioned only as background, citing other work.
• Main results:
  • Background cited by the authors: two earlier phase III trials found that cisplatin plus an antifolate (pemetrexed or raltitrexed) gave a 3-month median overall survival benefit over cisplatin alone (12.1 vs. 9.3 months, and 11.4 vs. 8.8 months).
  • In preliminary data from the randomized phase II portion of the French MAPS trial, the disease control rate at 6 months was 73.5% in the bevacizumab arm (bevacizumab plus cisplatin and pemetrexed) vs. 43.2% in the control arm.
  • In preliminary data from trial S0905 (cediranib plus pemetrexed and cisplatin), the 19 patients evaluable by modified RECIST had a response rate of 53% and a median progression-free survival of 10 months. Median overall survival for all patients was 16 months. One treatment-related death due to encephalopathy was reported.
  • In the same S0905 trial, Table 1 reports a response rate of 22% among 18 patients assessed by standard RECIST 1.1.
  • In trial MESOTREM-2008, 29 patients whose disease progressed after first-line platinum chemotherapy received tremelimumab. Two (7%) had a durable partial remission. The study did not meet its primary endpoint. Median progression-free survival was 6.2 months and median overall survival was 10.7 months.
  • In the ADAM trial (68 patients enrolled so far), median progression-free survival was 98 days with ADI-PEG20 vs. 59 days with best supportive care alone (P = 0.02).
  • In trial S0722 of everolimus (61 patients enrolled; preliminary data on 35), there were no responses by standard RECIST. Estimated median progression-free survival was 3 months and estimated median overall survival was 5 months. The authors described this as a lack of single-agent activity.
• The authors' conclusion: The authors concluded that cediranib has shown promising first-line activity and warrants further investigation, and that bevacizumab phase III results are pending. They wrote that tremelimumab induces durable remissions in some patients who need to be selected, and that there is still insufficient evidence to recommend second-line chemotherapy as standard. In their view, more novel agents are in trials than ever before, which brings hope of improvements in the next decade.

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: Pleural Mesothelioma, Clinical Trial, Prognosis, Median Overall Survival, Chemotherapy, Pemetrexed (Alimta), Cisplatin, Metastasis.

Related studies

• Systemic treatment of malignant pleural mesothelioma — F. Grosso, G.V. Scagliotti (2012)
• Estimating treatment effects from a randomized clinical trial in the presence of a secondary treatment — M. Zhang, Y. Wang (2012)
• Pemetrexed disodium in combination with cisplatin versus other cytotoxic agents or supportive care for the treatment of malignant pleural mesothelioma — J. Green, Y. Dundar, et al. (2007)
• Chemotherapy and targeted therapies for unresectable malignant mesothelioma — R.J. Kelly, E. Sharon, 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)
• Systemic chemotherapy with pemetrexed and cisplatin for malignant peritoneal mesothelioma: a single institution experience — G. Lainakis, F. Zagouri, et al. (2011)

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