Maintenance pemetrexed after platinum pemetrexed chemotherapy and survival outcomes in malignant pleural mesothelioma in a multicenter real world study

Our plain-English summary of Maintenance pemetrexed after platinum pemetrexed chemotherapy and survival outcomes in malignant pleural mesothelioma in a multicenter real world study, by O. Aydin, Z.S. Isleyen, M. Erciyestepe, et al (Scientific Reports, 2026).

The study

• Authors: O. Aydin, Z.S. Isleyen, M. Erciyestepe, A.E. Ozturk, S.D. Sonusen, T. Atasever, S. Cokgezer, E. Cicek, A.G.S. Durmaz, L.S. Can, G.B. Aykut, T. Baydas, M. Aydogan, S.A. Ersoy, M.M. Atci, K. Erturk
• Journal: Scientific Reports
• Published: 2026;16(1)
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis, and the role of maintenance therapy after first-line platinum-pemetrexed chemotherapy remains unclear. We conducted a multicenter retrospective study including 96 patients with metastatic or unresectable MPM treated across eight tertiary oncology centers. Eligible patients had received at least four cycles of first-line platinum-pemetrexed and achieved disease control, after which they were either administered maintenance pemetrexed (n = 54) or observed without further treatment (n = 42). Maintenance pemetrexed was associated with significantly prolonged median progression-free survival (15.5 vs. 7.9 months; p < 0.001) and overall survival (22.3 vs. 16.4 months; p = 0.002) compared with observation. Multivariate analyses confirmed maintenance pemetrexed as an independent predictor of improved progression-free survival (HR 2.92; 95% CI 1.81-4.72; p < 0.001) and overall survival (HR 2.10; 95% CI 1.24-3.55; p = 0.005). Non-epithelioid histology was independently associated with worse outcomes. Subgroup analyses demonstrated that the survival benefit of maintenance pemetrexed persisted in patients achieving both partial response and stable disease after first-line chemotherapy. Importantly, maintenance therapy was well tolerated, with no discontinuations due to toxicity, highlighting its feasibility in routine practice. These real-world findings suggest that maintenance pemetrexed may be associated with improved survival outcomes in patients with MPM who achieve disease control after first-line therapy.

© 2026. The Author(s).

In plain English

This retrospective study reviewed records from eight cancer referral centers in Istanbul, Turkey. It covered 96 patients with malignant pleural mesothelioma that was metastatic or could not be removed surgically, and whose disease had been controlled by at least four cycles of first-line platinum–pemetrexed chemotherapy. Afterwards, 54 received maintenance pemetrexed and 42 were observed without treatment. Doctors chose; it was not random. The study did not examine asbestos exposure. Median progression-free survival was 15.5 months with maintenance versus 7.9 with observation. Median overall survival was 22.3 versus 16.4 months. After adjustment, patients without maintenance had a higher risk of progression or death (hazard ratio 2.92, 95% confidence interval 1.81–4.72) and of death (hazard ratio 2.10, 95% confidence interval 1.24–3.55). Non-epithelioid tumors were linked to worse outcomes. The maintenance group had responded better to first-line chemotherapy. No patient stopped maintenance because of side effects, though these were not graded in detail. The authors concluded that maintenance pemetrexed may be a feasible option for selected patients, that the findings do not show cause and effect, and that randomized studies are needed.

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 cohort study using real-world clinical data; maintenance was not randomly assigned
• Who was studied: 96 patients with metastatic or unresectable malignant pleural mesothelioma, selected from approximately 390 screened at eight tertiary referral centers in Istanbul, Turkey. The study dates are not stated. All had received at least four cycles of first-line platinum–pemetrexed and achieved disease control. 32 of them had earlier undergone surgery and were later treated for recurrence. Mean age was 60.4 years, 82.3% had epithelioid histology, and median follow-up was 42.5 months.
• Exposure: Not an asbestos-exposure study. It compared maintenance pemetrexed (54 patients, at least four maintenance cycles) with observation without treatment (42 patients) after first-line platinum–pemetrexed chemotherapy.
• Main results:
  • Median progression-free survival was 15.5 months in the maintenance pemetrexed group versus 7.9 months in the no-maintenance group (p < 0.001).
  • Median overall survival was 22.3 months in the maintenance pemetrexed group versus 16.4 months in patients without maintenance (p = 0.002).
  • In multivariate analysis, with maintenance as the reference group, patients not receiving maintenance had a hazard ratio for progression or death (progression-free survival) of 2.92 (95% CI 1.81–4.72; p < 0.001).
  • In multivariate analysis, with maintenance as the reference group, patients not receiving maintenance had a hazard ratio for death of 2.10 (95% CI 1.24–3.55; p = 0.005).
  • Among patients with a partial response to first-line chemotherapy, median progression-free survival was 13.9 months with maintenance versus 8.9 months without (p = 0.005).
  • Among patients with stable disease after first-line chemotherapy, median progression-free survival was 19.5 months with maintenance versus 5.4 months without (p = 0.002).
  • Compared with epithelioid histology, non-epithelioid histology was independently associated with shorter progression-free survival (multivariate HR 1.90, 95% CI 1.04–3.46) and shorter overall survival (multivariate HR 3.12, 95% CI 1.59–6.13).
  • Response to first-line chemotherapy differed between the groups: partial response occurred in 48 of 54 (88.9%) maintenance patients versus 25 of 42 (59.5%) no-maintenance patients (p = 0.001).
  • No patient on maintenance pemetrexed needed permanent discontinuation or dose interruption because of toxicity. Detailed toxicity grading was not recorded.
  • At last follow-up, 31 patients (32.3%) were alive. Of the 15 alive without progression, 14 were receiving maintenance pemetrexed.
• The authors' conclusion: The authors concluded that maintenance pemetrexed after first-line platinum–pemetrexed was associated with improved progression-free and overall survival in patients who achieved disease control. They said it may be a feasible option for selected patients, but that prospective randomized studies are required to confirm this.
• Limitations the authors state:
  • The retrospective design carries a risk of selection bias and residual confounding.
  • Maintenance was not randomly assigned and was chosen by physicians, so the groups may have differed in unmeasured prognostic factors.
  • Some subgroup analyses may be underpowered.
  • Treatment decisions followed each institution's practices, so treatment strategies varied. Radiotherapy details were not consistently available.
  • Treatments given after progression may have influenced overall survival.
  • Toxicity grading and patient-reported outcomes were not systematically collected.
  • The authors stated that the findings should not be taken as evidence that maintenance pemetrexed causes improved survival.
  • Molecular profiling data were not available, so outcomes could not be assessed by molecular subgroup.

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: Pemetrexed (Alimta), Chemotherapy, Pleural Mesothelioma, Prognosis, Platinum-Pemetrexed, Unresectable, Progression-Free Survival, Overall Survival.

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• Feasibility of Tumor Treating Fields with Pemetrexed and Platinum-Based Chemotherapy for Unresectable Malignant Pleural Mesothelioma: Single-Center, Real-World Data — T. Kutuk, H. Appel, et al. (2022)
• Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma: A Case Report and Literatures Review — X.Q. Jing, L. Zhou, et al. (2016)
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