Benefit with first-line ICIs in mesothelioma

Our plain-English summary of Benefit with first-line ICIs in mesothelioma, by D. Romero (Nature Reviews. Clinical Oncology, 2021).

The study

• Author: D. Romero
• Journal: Nature Reviews. Clinical Oncology
• Published: 2021;18(4):194
• Type of article: Comment
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This is a one-page research highlight in which the author, Diana Romero, summarized a phase III trial called CheckMate 743, reported separately by Baas and colleagues (Lancet 2021). It is not original research. In the trial, 605 patients with unresectable malignant pleural mesothelioma were randomly assigned to the immunotherapy drugs nivolumab plus ipilimumab or to standard chemotherapy. Median overall survival was 18.1 months with immunotherapy versus 14.1 months with chemotherapy (HR 0.74, 96.6% CI 0.60–0.91; P = 0.002). The benefit was seen in all subgroups except patients aged 75 or older. In non-epithelioid mesothelioma, median survival was 18.1 versus 8.8 months. In epithelioid mesothelioma it was 18.7 versus 16.5 months (HR 0.86, 95% CI 0.69–1.08). Progression-free survival did not differ significantly, and response rates were similar (40% versus 43%). Grade 3–4 treatment-related side effects occurred in 30% of the immunotherapy group and 32% of the chemotherapy group. There were 3 versus 1 treatment-related deaths. The author wrote that the regimen should be considered a new standard of care. Asbestos exposure was not discussed.

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: Research highlight (short news summary) of a multicentre, randomised, open-label phase III trial (CheckMate 743, Baas et al., Lancet 2021); not original research by the highlight's author
• Who was studied: 605 patients with unresectable malignant pleural mesothelioma (MPM) in the CheckMate 743 trial; locations and dates are not given in the highlight
• Exposure: Treatment, not asbestos: first-line nivolumab plus ipilimumab (immune-checkpoint inhibitors) compared with standard chemotherapy. The highlight describes the standard as platinum agents with pemetrexed.
• Main results:
  • Median overall survival was 18.1 months with nivolumab plus ipilimumab versus 14.1 months with chemotherapy (HR 0.74, 96.6% CI 0.60–0.91; P = 0.002)
  • The overall survival benefit was observed across all subgroups except patients aged 75 years or older (HR 1.02, 96.6% CI 0.70–1.48)
  • In patients with non-epithelioid MPM, median overall survival was 18.1 months with immunotherapy versus 8.8 months with chemotherapy (HR 0.46, 95% CI 0.31–0.68)
  • In patients with epithelioid MPM, median overall survival was 18.7 months with immunotherapy versus 16.5 months with chemotherapy (HR 0.86, 95% CI 0.69–1.08)
  • Among patients receiving immunotherapy, median overall survival was 18.0 months for PD-L1 tumour expression of 1% or more and 17.3 months for less than 1%
  • Median progression-free survival was 6.8 months with immunotherapy and 7.2 months with chemotherapy. The difference was not significant (HR 1.00, 95% CI 0.82–1.21).
  • Objective response rates were similar: 40% with immunotherapy versus 43% with chemotherapy. Only patients receiving immunotherapy had complete responses (2%).
  • Grade 3–4 treatment-related adverse events occurred in 30% of the immunotherapy group and 32% of the chemotherapy group. There were 3 versus 1 treatment-related deaths.
  • The FDA approved nivolumab plus ipilimumab in October 2020 for first-line treatment of unresectable MPM based on these results
• The authors' conclusion: The highlight's author (not the trial authors) wrote that the regimen should be considered a new standard of care for these patients. The author also wrote that studies to identify predictive biomarkers, particularly in epithelioid MPM, are warranted.

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: Mesothelioma.

Related studies

• A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol — N. Fujimoto, K. Aoe, et al. (2018)
• NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma — V.D. Haakensen, A.K. Nowak, et al. (2021)
• Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in — A.K. Nowak, W.J. Lesterhuis, et al. (2020)
• Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial — G.L. Ceresoli, J.G. Aerts, et al. (2019)
• Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study — N. Katirtzoglou, I. Gkiozos, et al. (2010)
• Switch-maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma (NVALT19): an investigator-initiated, randomised, open-label, phase 2 trial — C.J. de Gooijer, V. van der Noort, et al. (2021)

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