Immunotherapy in relapsed mesothelioma

Our plain-English summary of Immunotherapy in relapsed mesothelioma, by S. Brosseau, X. Dhalluin, G. Zalcman, et al (Immunotherapy, 2018).

The study

• Authors: S. Brosseau, X. Dhalluin, G. Zalcman, A. Scherpereel
• Journal: Immunotherapy
• Published: 2018;10(2):77-80
• Type of article: Editorial
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this editorial, the authors reviewed immunotherapy, particularly immune checkpoint inhibitors (ICI), as treatment for malignant pleural mesothelioma (MPM) that had relapsed after first-line chemotherapy. They noted that MPM arises mainly after occupational asbestos exposure, that its prognosis remains poor, and that no second-line treatment had been approved. They summarized published and conference-reported trials. Early studies of the anti-PD-1 antibodies pembrolizumab and nivolumab and the anti-PD-L1 antibody avelumab reported disease control rates of 50% to 80%. In contrast, the anti-CTLA-4 antibody tremelimumab did not significantly improve outcome over placebo in the DETERMINE trial of 571 patients (median overall survival 7.7 versus 7.3 months). In the French Phase II MAPS-2 trial, disease control at 12 weeks was 50.0% with nivolumab plus ipilimumab and 44.4% with nivolumab alone. Three treatment-related deaths occurred in the combination arm. A Swiss registry of 48 patients given pembrolizumab reported an objective response rate of 25%, with better results in patients whose tumors expressed PD-L1. The authors concluded that these studies, totalling more than 250 patients, showed significant activity of ICI with acceptable toxicity. They discussed ongoing Phase III trials and possible ethical issues with placebo arms. They also noted that no ideal biomarker yet identified the patients most likely to benefit.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This editorial, not an original study, reviewed immunotherapy results, mainly checkpoint inhibitors, in malignant pleural mesothelioma, focusing on disease that relapsed after chemotherapy; one trial included first-line patients. Occupational asbestos exposure, named as the disease's main origin, was not studied. In MAPS-2 (63 patients given nivolumab, 62 nivolumab plus ipilimumab), 12-week disease control among the first 108 eligible patients was 50.0% with the combination and 44.4% with nivolumab alone. After a median 15-month follow-up, median overall survival was 13.6 months (95% CI 6.7 to not reached) with nivolumab alone and not reached with the combination. Three combination-arm deaths were judged treatment-related. In DETERMINE (571 patients), tremelimumab did not significantly improve outcome over placebo: median survival 7.7 months (95% CI 6.8 to 8.9) versus 7.3 months (95% CI 5.9 to 8.7). A Swiss registry of 48 pembrolizumab patients reported a 25% response rate and median survival of 7.2 months. The authors concluded that these studies, totaling more than 250 patients, showed significant activity of checkpoint inhibitors with acceptable toxicity. They noted no ideal biomarker yet identifies who benefits most.

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: Editorial: a narrative overview of other clinical trials and a registry of immunotherapy in malignant pleural mesothelioma, mainly in relapsed disease
• Who was studied: Patients with malignant pleural mesothelioma in the trials and registry discussed, mostly after prior chemotherapy. The NIBIT Meso 1 trial also included first-line patients. The MAPS-2 trial enrolled patients with unresectable disease that progressed after one or two prior lines of chemotherapy including pemetrexed/platinum: 63 received nivolumab and 62 received nivolumab plus ipilimumab.
• Exposure: Not an asbestos exposure study. The treatments discussed were immunotherapy drugs: nivolumab, ipilimumab, pembrolizumab, avelumab, tremelimumab and durvalumab. Asbestos is mentioned only as background, with occupational exposure named as the main origin of the disease. No fiber types are named.
• Main results:
  • As background, the authors stated that almost all experimental therapies tested as second-line or later treatment before immunotherapy had disease control rates at 3 months below 30%. Median overall survival in those trials was 6 to 9 months.
  • DETERMINE trial (571 patients, reported by other investigators): tremelimumab did not significantly improve outcome compared with placebo in second- and third-line patients. The hazard ratio was 0.92 (95% CI 0.76 to 1.12), p = 0.41.
  • DETERMINE trial: median overall survival was 7.7 months (95% CI 6.8 to 8.9) with tremelimumab versus 7.3 months (95% CI 5.9 to 8.7) with placebo.
  • MAPS-2 trial: the primary end point was disease control at 12 weeks in the first 108 eligible patients, as centrally assessed. Disease control was 50.0% in the nivolumab plus ipilimumab arm and 44.4% in the nivolumab arm. The editorial described these rates as higher than historical data.
  • MAPS-2 updated results, after a median follow-up of 15 months: median overall survival was 13.6 months (95% CI 6.7 to not reached) in the nivolumab-alone arm and was not reached in the combination arm.
  • MAPS-2: median progression-free survival was 5.6 months (95% CI 3.2 to 8.4) for nivolumab plus ipilimumab and 4.0 months (95% CI 2.8 to 5.7) for nivolumab alone.
  • MAPS-2: in the combination arm, three deaths were deemed treatment-related. They were due to fulminant hepatitis, encephalitis and acute kidney failure.
  • Swiss registry of 48 patients given pembrolizumab: one patient had a complete response and 11 had partial responses, giving an objective response rate of 25%.
  • Swiss registry: the disease control rate was 52%. Median progression-free survival was 3.6 months and median overall survival was 7.2 months.
  • Swiss registry: seven patients (15%) stopped pembrolizumab because of adverse events.
  • NIBIT Meso 1 trial of durvalumab plus tremelimumab: patients received it as first-line (30%) or second-line (70%) treatment. The immune-related objective response rate was 27.5% and median overall survival was 15.3 months.
• The authors' conclusion: The authors concluded that the studies they reviewed, totaling more than 250 patients, showed significant activity of immune checkpoint inhibitors with acceptable toxicity.
• Limitations the authors state:
  • The authors stated that PD-L1 biomarker studies gave conflicting results. They added that there is currently no ideal biomarker to identify which patients benefit most from checkpoint inhibitors.

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, Pleural Mesothelioma, Chemotherapy, Asbestos Exposure, Prognosis, Pembrolizumab (Keytruda).

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• Multimodality treatment of malignant pleural mesothelioma with or without immunotherapy: does it change anything? — M. Lucchi, A. Picchi, et al. (2010)
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