Immunotherapy trials in mesothelioma - promising results, but don't stop here

Our plain-English summary of Immunotherapy trials in mesothelioma - promising results, but don't stop here, by A.K. Nowak, P.M. Forde (Nature Reviews. Clinical Oncology, 2019).

The study

• Authors: A.K. Nowak, P.M. Forde
• Journal: Nature Reviews. Clinical Oncology
• Published: 2019;16(12):726-728
• Type of article: Comment
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In the past few years, several studies have addressed the possibility of using immunotherapies to treat patients with mesothelioma. Herein, we discuss two recent trials, one testing the immune-checkpoint inhibitor nivolumab and the other testing a mesothelin-directed therapeutic vaccine, and reflect on the advances and challenges remaining in this research area.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

In plain English

This article was a short commentary, not a new study. The authors discussed two trials by other research groups in patients with malignant pleural mesothelioma. In the MERIT trial reported by Okada and colleagues, 34 patients whose disease had resisted or failed standard chemotherapy received the drug nivolumab. Ten (29%) had an objective response. Median progression-free survival was 6.1 months and median overall survival was 17.3 months. In the trial reported by Hassan and colleagues, patients received a mesothelin-targeted vaccine, CRS-207, together with cisplatin and pemetrexed chemotherapy. Of 35 evaluable patients, 20 (57%) had an objective response. Median progression-free survival was 7.5 months and median overall survival was 14.7 months. The authors noted that CRS-207 is no longer in development because a later trial was negative. They cautioned that single-arm trials are hard to interpret and can favour long survival when selected patients seek treatment at specialist centres. The authors concluded that single-agent checkpoint blockade is most likely a step forward, but that patients still need better treatments.

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: Commentary (News & Views) discussing two published single-arm clinical trials by other researchers; not original research by these authors
• Who was studied: Patients with malignant pleural mesothelioma in two trials by others. MERIT (Okada et al., Japan): 34 patients with advanced-stage disease resistant to or refractory to standard chemotherapy. Hassan et al.: 37 eligible patients with surgically unresectable epithelioid or epithelioid-predominant biphasic mesothelioma.
• Exposure: Not an asbestos exposure study. Asbestos is mentioned only as the main cause of the disease. The treatments discussed were nivolumab given alone as second or later therapy (MERIT), and the CRS-207 vaccine given before and after cisplatin plus pemetrexed chemotherapy (Hassan et al.).
• Main results:
  • MERIT trial (nivolumab, Okada et al.): 10 of 34 patients (29%) had an objective response.
  • MERIT trial: median progression-free survival was 6.1 months, duration of response 11.1 months, and overall survival 17.3 months.
  • MERIT trial: 4 patients stopped treatment because of adverse events. These included 2 with interstitial pneumonia (one grade 2, one grade 3) and 2 with grade 3 pneumonitis.
  • CRS-207 trial (Hassan et al.): of 35 evaluable patients, 20 (57%) had an objective response. The median duration of response was 5.0 months.
  • CRS-207 trial: median progression-free survival was 7.5 months. The authors said this compared favourably with historic figures of 4.7 to 7.0 months for cisplatin plus pemetrexed. They called the median overall survival of 14.7 months relatively modest.
  • CRS-207 is no longer in clinical development because a later-phase trial was negative.
• The authors' conclusion: The authors concluded that single-agent checkpoint blockade is most likely a step forward, but that patients with malignant pleural mesothelioma still need better treatments that substantially improve outcomes. They also said the CRS-207 results support mesothelin-directed immunotherapy as an approach warranting further investigation.
• Limitations the authors state:
  • The authors said single-arm phase II studies are hard to interpret. Survival can look longer when selected patients seek treatment at single specialist centres.
  • In the CRS-207 trial, the vaccine was given both before and after chemotherapy. Because of this sequential design, the apparent immune-related response pattern might reflect different responses to the vaccine and to chemotherapy.
  • The authors noted that results of checkpoint inhibitors in real-world practice have not been as promising as in trials.

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: Immunotherapy, Mesothelioma, checkpoint inhibitors, Nivolumab (Opdivo), Mesothelin.

Related studies

• Promising investigational drug candidates in phase I and phase II clinical trials for mesothelioma — A. Guazzelli, E. Bakker, et al. (2017)
• Serum soluble mesothelin-related protein (SMRP) and fibulin-3 levels correlate with baseline malignant pleural mesothelioma (MPM) tumor volumes but are not useful as biomarkers of response in an immunotherapy trial — S.I. Katz, L. Roshkovan, et al. (2021)
• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial — N.L. de Boer, J.P. van Kooten, et al. (2019)
• Malignant mesothelioma clinical trial combines immunotherapy drugs — M.S. Chatwal, T. Tanvetyanon (2018)
• Immunotherapy for mesothelioma: a critical review of current clinical trials and future perspectives — S.G. Gray, L. Mutti (2020)
• Network analysis of immunotherapy-induced regressing tumours identifies novel synergistic drug combinations — W.J. Lesterhuis, C. Rinaldi, et al. (2015)

Browse more research in Nature Reviews. Clinical Oncology, or return to medical research.