Follow-up after first-Line nivOlumab plus ipilimumab in patients with diffuse pleuRal mesotheliomA: a real-world Dutch cohort study-FLORA

Our plain-English summary of Follow-up after first-Line nivOlumab plus ipilimumab in patients with diffuse pleuRal mesotheliomA: a real-world Dutch cohort study-FLORA, by L.H. Douma, M.M. Hofman, F. Zwierenga, et al (ESMO Open, 2025).

The study

• Authors: L.H. Douma, M.M. Hofman, F. Zwierenga, T.M.T. Zondervan, A.I.G. Buma, H. Schouwink, D.W. Dumoulin, J.A. Burgers, I. Smesseim, J.G.J.V. Aerts, C.J. de Gooijer
• Journal: ESMO Open
• Published: 2025;10(2):104123
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Diffuse pleural mesothelioma (dPM) is an aggressive malignancy, primarily treated with palliative systemic therapy. Since 2022, nivolumab-ipilimumab (nivo/ipi) has replaced chemotherapy as the standard first-line treatment for dPM in the Netherlands. Chemotherapy remains a rational second-line treatment. The real-world effectiveness of second-line treatment after doublet immunotherapy remains unknown. The FLORA study aimed to provide an overview of treatment patterns in patients with dPM after first-line nivo/ipi and evaluate the effectiveness of second-line chemotherapy based on real-world data.

Patients And Methods: FLORA was a Dutch multicenter retrospective cohort study. Clinical data were collected from the medical records. The primary endpoints were treatment patterns after nivo/ipi and median overall survival (mOS) of patients receiving second-line chemotherapy. The secondary endpoints were objective response rate (ORR), median progression-free survival (mPFS) of second-line chemotherapy, and subgroup analyses (Eastern Cooperative Oncology Group performance status and histological subtype). The study also updated the mOS for first-line nivo/ipi patients.

Results: Between May 2021 and July 2023, 277 patients with dPM receiving first-line nivo/ipi therapy were included. Sixty-eight percent of the patients were male, with a median age of 72 years (interquartile range 67-77 years). The histological subtypes were epithelioid (62%), sarcomatoid (22%), biphasic (13%), and unknown (3%). One hundred and two (47%) of the 218 patients with disease progression received second-line treatment, of whom 83 received second-line platinum-pemetrexed chemotherapy. The mOS and mPFS for second-line chemotherapy were 8.2 months ([95% confidence interval (CI) 7.4-9.1 months] and 5.6 months (95% CI 4.9-6.3 months), respectively, with an ORR of 37%. Poor performance score was the main reason for not receiving second-line treatment.

Conclusion: This study provides the first real-world data on subsequent treatment of patients with dPM with disease progression on nivo/ipi, resulting in an mOS of 8.2 months after second-line chemotherapy.

Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

In plain English

This Dutch retrospective cohort study reviewed the medical records of 277 adults with diffuse pleural mesothelioma at six hospitals. All had received nivolumab plus ipilimumab immunotherapy as their first treatment between January 2021 and July 2023. The study did not examine asbestos exposure. Median overall survival from the start of this treatment was 14.6 months (95% CI 12.7-16.5 months). Of 218 patients whose disease progressed, 102 (47%) received a second treatment, and 83 of them got platinum-pemetrexed chemotherapy. Poor performance status (reduced ability to carry out daily activities) was the most common reason for no second treatment, affecting 62 patients. In the 83 patients given second-line chemotherapy, median overall survival was 8.2 months (95% CI 7.4-9.1 months) and median progression-free survival was 5.6 months (95% CI 4.9-6.3 months). A partial response was seen in 31 of the 83 (37%; 95% CI 27% to 49%), and none had a complete response. The authors concluded that second-line chemotherapy could be a rational option after nivolumab plus ipilimumab and called for further research. They noted that the study was retrospective, had a single arm and could not correct for all confounders.

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: Multicenter retrospective observational cohort study using medical records (real-world data)
• Who was studied: 277 adults with unresectable diffuse pleural mesothelioma (peritoneal mesothelioma excluded) treated with first-line nivolumab plus ipilimumab at six Dutch hospitals, January 2021 to July 2023. The authors estimate this covers about 80% of eligible Dutch patients. The follow-up cut-off was 1 May 2024.
• Exposure: No asbestos exposure was studied. The study examined treatment: first-line nivolumab 360 mg (or 4.5 mg/kg) every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks. Some patients then received second-line platinum-pemetrexed chemotherapy, mostly carboplatin-pemetrexed.
• Main results:
  • Of all 277 patients, 218 (79%) had disease progression on first-line nivolumab plus ipilimumab.
  • Of the 218 patients with progression, 102 (47%) received second-line treatment.
  • 83 patients received second-line platinum-based/pemetrexed chemotherapy, which is 38% of all patients with progressive disease.
  • 106 patients with progression received no second-line treatment. Of these, 62 (59%) were ineligible because of poor performance status.
  • For the 83 patients on second-line chemotherapy, median overall survival was 8.2 months (95% CI 7.4-9.1 months), measured from the first chemotherapy dose.
  • For the same group, median progression-free survival on second-line chemotherapy was 5.6 months (95% CI 4.9-6.3 months).
  • The objective response rate to second-line chemotherapy was 37% (95% CI 27% to 49%). This came from 31 partial responses; no patient had a complete response.
  • For all 277 patients, median overall survival from the start of first-line nivolumab plus ipilimumab was 14.6 months (95% CI 12.7-16.5 months).
  • For all 277 patients, median progression-free survival on first-line nivolumab plus ipilimumab was 5.5 months (95% CI 4.8-6.3 months).
  • Among second-line chemotherapy patients, median overall survival differed by performance status. It was 12.3 months (95% CI 9.0-15.6) for status 0 (n = 20), 8.0 months (95% CI 7.5-8.5) for status 1, and 7.4 months (95% CI 4.8-10.0) for status 2. The authors state that retrospective analysis does not allow a formal statistical comparison.
  • Median overall survival on second-line chemotherapy by histological subtype was 9.5 months (95% CI 7.5-11.5) for epithelioid (n = 54), 7.8 months (95% CI 6.9-8.6) for sarcomatoid (n = 14), and 8.2 months (95% CI 7.6-8.7) for biphasic (n = 15).
  • 14 patients died without disease progression. Seven of them died of grade 5 (fatal) toxicity from nivolumab plus ipilimumab.
  • 66 second-line chemotherapy patients had progressive disease at the cut-off date. Of these, 16 (24%) received third-line treatment.
• The authors' conclusion: The authors concluded that second-line chemotherapy could be a rational option for patients with diffuse pleural mesothelioma pretreated with nivolumab plus ipilimumab. They recommended further research using more extensive meta-analyses to confirm this observation.
• Limitations the authors state:
  • In a minority of cases, best overall response was established retrospectively by a pulmonologist, potentially introducing bias.
  • CT scans were not done at the same time points; they followed standard-of-care schedules.
  • The authors could not correct for all potential confounders.
  • The study was retrospective and single-arm.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Ipilimumab (Yervoy), Pleural Mesothelioma, Cohort Study, Palliative Care, Systemic Therapy, Chemotherapy, Immunotherapy.

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