Novel therapies for malignant pleural mesothelioma

Our plain-English summary of Novel therapies for malignant pleural mesothelioma, by A. Scherpereel, F. Wallyn, S.M. Albelda, et al (The Lancet. Oncology, 2018).

The study

• Authors: A. Scherpereel, F. Wallyn, S.M. Albelda, C. Munck
• Journal: The Lancet. Oncology
• Published: 2018;19(3):e161-e172
• Type of article: Review
• Cited by: 112 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is a rare cancer that is typically associated with exposure to asbestos. Patients with malignant pleural mesothelioma have poor outcomes with suboptimal therapeutic options and currently no treatment is curative. The standard frontline treatment, cisplatin plus pemetrexed chemotherapy, has only short and insufficient efficacy, and no validated treatment beyond first-line therapy is available. New therapeutic strategies are therefore needed. The addition of bevacizumab (an anti-VEGF antibody) combined with cisplatin plus pemetrexed has shown some promise. However, immunotherapy, especially immune checkpoint inhibitors, has generated a lot of excitement because of data suggesting the potential value of immune checkpoint inhibitors for patients who have failed chemotherapy. In this Review, we describe immune checkpoint inhibitors, other immunotherapies, targeted therapies, or combinations of novel drugs being investigated in malignant pleural mesothelioma, as well as the issues surrounding the selection of the best candidates for these treatments.

Copyright © 2018 Elsevier Ltd. All rights reserved.

In plain English

This article was a narrative review, which the authors stated could not be considered a systematic review. They searched PubMed, oncology meeting proceedings (2000 to September 2017, English only) and ClinicalTrials.gov for malignant pleural mesothelioma treatments; the article described this cancer as typically associated with asbestos exposure. Standard pemetrexed plus platinum chemotherapy, the review noted, gave median overall survival not exceeding 13–16 months. The trials it summarized included these. In the MAPS trial of 448 patients, adding bevacizumab to first-line cisplatin plus pemetrexed, with bevacizumab maintenance in patients without progression, gave median overall survival of 18.82 versus 16.07 months with chemotherapy alone (HR 0.67; 95% CI 0.61–0.94). The DETERMINE trial (n=564) found no benefit for tremelimumab over placebo. In the MAPS-2 trial of 125 relapsed patients, 12-week disease control was 44% with nivolumab and 50% with nivolumab plus ipilimumab, with more severe side effects in the combination group. The authors concluded that targeted therapies and immunotherapy might soon be a reality for these patients. They cautioned that immune checkpoint therapy data were still incomplete and based on non-randomised studies.

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 (non-systematic) review of published trials and registered clinical trials of targeted therapies and immunotherapies for malignant pleural mesothelioma
• Who was studied: Published literature found through PubMed and proceedings of major oncology meetings from Jan 1, 2000, to Sept 27, 2017, plus a search of ClinicalTrials.gov for malignant pleural mesothelioma trials
• Exposure: Not an exposure study. The review concerns drug treatments. Asbestos appears only as background: the article describes malignant pleural mesothelioma as typically associated with asbestos exposure.
• Main results:
  • From earlier trials cited by the review: median overall survival with standard pemetrexed plus platinum chemotherapy does not exceed 13–16 months
  • From the MAPS trial (448 patients, cited by the review): adding bevacizumab to cisplatin plus pemetrexed as first-line treatment, with bevacizumab maintenance in non-progressive patients, gave median overall survival of 18.82 months versus 16.07 months with chemotherapy alone (HR 0.67; 95% CI 0.61–0.94; p=0.015)
  • From a phase 2 nintedanib trial of 87 patients (cited by the review): in patients with epithelioid histology, median progression-free survival was 9.7 months with nintedanib versus 5.7 months with placebo (HR 0.49; 95% CI 0.30–0.82; p=0.006). The overall survival difference was not statistically significant.
  • From the DETERMINE trial (n=564, cited by the review): tremelimumab versus placebo as second-line or third-line treatment showed no benefit (median overall survival 7.7 months versus 7.3 months, p=0.408)
  • From the KEYNOTE-028 phase 1b trial (25 patients with PD-L1-expressing tumours, cited by the review): 20% of patients given pembrolizumab had an objective response (95% CI 6.8–40.7)
  • From the MAPS-2 trial (125 relapsed patients, cited by the review): disease control after 12 weeks occurred in 44% of patients in the nivolumab group and 50% in the nivolumab plus ipilimumab group
  • From the MAPS-2 trial: grade 3–4 drug-related adverse events occurred in 26.2% of the combination group versus 12.7% of the nivolumab group, and three treatment-related deaths were reported in the nivolumab plus ipilimumab group
• The authors' conclusion: The authors concluded that targeted therapies and immunotherapy might soon be a reality for patients with malignant pleural mesothelioma, and that better ways to identify which patients benefit are needed
• Limitations the authors state:
  • The authors state the review is not a systematic review of the literature
  • Only English-language papers were included
  • The authors state that available data on immune checkpoint therapy were still incomplete and based on non-randomised studies

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, Cisplatin, Pemetrexed (Alimta), Chemotherapy, First-line Therapy, Bevacizumab, Immunotherapy, checkpoint inhibitors.

Related studies

• Targeted therapies in malignant pleural mesothelioma: a review of clinical studies — L. Greillier, S. Marco, et al. (2011)
• A review of bevacizumab in the treatment of malignant pleural mesothelioma — S. Brosseau, S. Assoun, et al. (2017)
• Novel targeted therapies and vaccination strategies for mesothelioma — M. Bagia, A.K. Nowak (2011)
• Immune checkpoint inhibition in malignant mesothelioma: Does it have a future? — A.S. Mansfield (2017)
• NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial — V. Gregorc, R.M. Gaafar, et al. (2018)
• Targeting the vasculature: anti-angiogenic agents for malignant mesothelioma — P.L. Chia, P.A. Russell, et al. (2016)

Browse more research in The Lancet. Oncology, or return to medical research.