Real-world outcomes of first-line immunotherapy and subsequent systemic therapies in pleural mesothelioma: a multicenter study in China

Our plain-English summary of Real-world outcomes of first-line immunotherapy and subsequent systemic therapies in pleural mesothelioma: a multicenter study in China, by B. Tian, B. Sun, Z. Zhou, et al (Translational Lung Cancer Research, 2025).

The study

• Authors: B. Tian, B. Sun, Z. Zhou, S. Kuang, J. Li, W. Pan, Z. Zhu, X. Si, L. Zhang, J. Liu, J. Shi, F. Wu, H. Zhao, H. Wang
• Journal: Translational Lung Cancer Research
• Published: 2025;14(12):5465-5478
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) has a poor prognosis, and immune checkpoint inhibitors (ICIs) have reshaped first-line therapy. However, real-world data comparing first-line immunotherapy with chemotherapy ± targeted therapy and defining optimal second-line strategies in Chinese patients remain limited. This multicenter retrospective real-world study aimed to compare survival outcomes between first-line immunotherapy and chemotherapy-based regimens and to evaluate the effectiveness of different subsequent systemic therapies in patients with PM.

Methods: This multicenter retrospective real-world cohort included patients with pathologically confirmed PM who received at least one line of systemic therapy at tertiary hospitals in China between January 2015 and January 2025. Patients were grouped by first-line regimen (immunotherapy vs. chemotherapy ± targeted therapy). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Generalized propensity scores with overlap weighting (OW) were used to balance baseline covariates, followed by weighted Kaplan-Meier and Cox regression analyses. For post-first-line analyses, chemo-start and immuno-start cohorts were used to compare OS across second-line chemotherapy, chemo-immunotherapy, and dual immunotherapy. Hazard ratio (HR), 95% confidence interval (CI), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were reported.

Results: Seventy-eight patients were included (chemotherapy ± targeted, n=50; immunotherapy, n=28; median follow-up, 35.7 months). After weighting, first-line immunotherapy improved OS vs. chemotherapy ± targeted therapy (weighted HR, 0.47; 95% CI: 0.23-0.95) and showed a trend toward longer PFS (weighted HR, 0.64; 95% CI: 0.34-1.17). OS benefit was greater in patients with ECOG PS 0-1 (HR, 0.44; 95% CI: 0.21-0.93), non-epithelioid histology (HR, 0.30; 95% CI: 0.10-0.97), or no prior radiotherapy (HR, 0.29; 95% CI: 0.12-0.68). In multivariate models, first-line immunotherapy (HR, 0.34; 95% CI: 0.13-0.90) and prior radiotherapy (HR, 0.35; 95% CI: 0.14-0.86) were independent protective factors for OS. ORR and DCR were similar between groups, and immune-related adverse events occurred in 14/28 (50.0%) immunotherapy patients, mostly grade 1-2, with no immune-related deaths. In the chemo-start cohort, second-line dual immunotherapy improved OS vs. chemo-immunotherapy (HR, 0.13; 95% CI: 0.03-0.62) but not vs. chemotherapy alone (HR, 0.43; 95% CI: 0.17-1.11), and chemo-immunotherapy did not differ from chemotherapy (HR, 2.08; 95% CI: 0.94-4.57). In the smaller immuno-start cohort, no significant OS differences were seen between second-line strategies (weighted Cox P=0.31).

Conclusions: In this multicenter real-world Chinese cohort, first-line immunotherapy was associated with a clinically meaningful OS improvement in PM, particularly among patients with good PS, non-epithelioid histology, or no prior radiotherapy. Dual immunotherapy may be a promising second-line option after chemotherapy, warranting confirmation in larger prospective studies.

© AME Publishing Company.

In plain English

This retrospective study reviewed records of 78 adults with pleural mesothelioma given drug treatment at three Chinese hospitals between 2015 and 2025. It compared 50 patients first given chemotherapy, with or without targeted therapy, with 28 first given immunotherapy. Weighting balanced measured baseline characteristics; the authors noted residual confounding and selection bias could remain. Asbestos exposure was documented in 8 of the 50 and 2 of the 28. Unweighted median overall survival was 15.4 months (95% CI 13.3 to 21.6) with chemotherapy and 35.8 months (95% CI 18.6 to not reached) with immunotherapy. After weighting, immunotherapy's hazard ratio for death was 0.47 (95% CI 0.23 to 0.95). Progression-free survival did not differ significantly, and response rates were similar. Immune-related side effects affected 14 of 28 immunotherapy patients, mostly grade 1 to 2, without immune-related deaths. After first-line chemotherapy, 6 patients given dual immunotherapy had longer overall survival than 8 given chemo-immunotherapy (HR 0.13, 95% CI 0.03 to 0.62). Versus chemotherapy alone, it was not statistically significant. The authors called later-line analyses exploratory, given small numbers.

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 real-world cohort study using medical records, with overlap weighting based on propensity scores to balance measured baseline covariates
• Who was studied: 78 adults with pathologically confirmed pleural mesothelioma who received systemic therapy between January 2015 and January 2025 at three tertiary hospitals in China (Peking Union Medical College Hospital, The First Affiliated Hospital of Guangzhou Medical University, The Second Xiangya Hospital). 50 were in the chemotherapy with or without targeted therapy group and 28 were in the immunotherapy group.
• Exposure: The exposure compared was treatment: first-line chemotherapy with or without targeted therapy versus first-line immunotherapy (immune checkpoint inhibitors). After progression, the study compared second-line chemotherapy, chemo-immunotherapy and dual immune checkpoint inhibition. Documented asbestos exposure was recorded only as a background covariate, and no fiber types were reported.
• Main results:
  • Documented asbestos exposure was 8 of 50 (16.0%) in the chemotherapy with or without targeted therapy group and 2 of 28 (7.1%) in the immunotherapy group.
  • Unweighted median overall survival was 15.4 months (95% CI 13.3 to 21.6) in the chemotherapy with or without targeted therapy group and 35.8 months (95% CI 18.6 to not reached) in the immunotherapy group.
  • After overlap weighting, first-line immunotherapy was associated with longer overall survival than chemotherapy with or without targeted therapy (weighted HR 0.47; 95% CI 0.23 to 0.95).
  • Unweighted median progression-free survival was 8.3 months in the chemotherapy with or without targeted therapy group and 12.2 months in the immunotherapy group. The difference was not significant (log-rank P=0.09).
  • The weighted HR for progression-free survival with immunotherapy versus chemotherapy with or without targeted therapy was 0.64 (95% CI 0.34 to 1.17), which was not statistically significant.
  • In subgroups, the overall survival benefit of immunotherapy was more pronounced in patients with ECOG PS 0 to 1 (HR 0.44; 95% CI 0.21 to 0.93), no history of radiotherapy (HR 0.29; 95% CI 0.12 to 0.68) and non-epithelioid histology (HR 0.30; 95% CI 0.10 to 0.97).
  • In multivariable analysis, first-line immunotherapy (HR 0.34; 95% CI 0.13 to 0.90; P=0.03) and radiotherapy (HR 0.35; 95% CI 0.14 to 0.86; P=0.02) were independent protective factors for overall survival.
  • The objective response rate was 39.3% with immunotherapy and 40.0% with chemotherapy. The disease control rate was 64.3% and 60.0%. None of these differences were statistically significant.
  • 14 of 28 (50.0%) immunotherapy patients had immune-related adverse events, mostly grade 1 to 2, with no immune-related deaths.
  • In the chemo-start cohort, second-line treatment was chemotherapy (n=36), chemo-immunotherapy (n=8) or dual immunotherapy (n=6).
  • In the chemo-start cohort, dual immunotherapy was associated with longer overall survival than chemo-immunotherapy (HR 0.13; 95% CI 0.03 to 0.62; P=0.01). The difference versus chemotherapy alone was not statistically significant (HR 0.43; 95% CI 0.17 to 1.11; P=0.08).
  • In the chemo-start cohort, chemo-immunotherapy did not differ significantly from chemotherapy (HR 2.08; 95% CI 0.94 to 4.57; P=0.07).
  • In the immuno-start cohort, 12 patients received later therapy (chemotherapy n=5, chemo-immunotherapy n=3, dual immunotherapy n=4). There were no significant differences in overall survival (weighted Cox P=0.31).
• The authors' conclusion: The authors concluded that, in their Chinese cohort, first-line immunotherapy improved overall survival in pleural mesothelioma compared with chemotherapy with or without targeted therapy, with limited effect on progression-free survival and response rates.
• Limitations the authors state:
  • The overall sample size was modest, especially in later-line subgroups, giving limited statistical power and wide confidence intervals.
  • Treating physicians chose treatments, so residual confounding and selection bias may remain despite weighting and adjustment.
  • Different drugs were grouped within each treatment category, which may have obscured the effects of specific regimens.
  • The post-progression analyses should be viewed as exploratory.
  • Asbestos exposure history was not collected in a standard way in earlier cases and may be incompletely documented.
  • Biomarker data such as PD-L1 expression or tumor mutational burden were not systematically available.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Pleural Mesothelioma, Prognosis, checkpoint inhibitors, First-line Therapy, Chemotherapy, Targeted Therapy, Systemic Therapy.

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