Comparative effectiveness of second-line immune checkpoint inhibitor therapy versus chemotherapy for malignant pleural mesothelioma

Our plain-English summary of Comparative effectiveness of second-line immune checkpoint inhibitor therapy versus chemotherapy for malignant pleural mesothelioma, by R.Y. Kim, Y. Li, M.E. Marmarelis, et al (Lung Cancer, 2021).

The study

• Authors: R.Y. Kim, Y. Li, M.E. Marmarelis, A. Vachani
• Journal: Lung Cancer
• Published: 2021;159:107-110
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Second-line immune checkpoint inhibition (ICI) was recently shown to have a survival advantage over placebo in malignant pleural mesothelioma (MPM), but the survival comparison to chemotherapy in patients with MPM receiving routine clinical care is unknown. Our objective was to examine the effectiveness of second-line ICI versus chemotherapy on overall survival (OS) outcomes in real-world patients with advanced MPM.

Materials And Methods: We performed a multicenter retrospective cohort study of real-world adult patients with advanced MPM who received first-line platinum-based chemotherapy and at least two total lines of systemic therapy. Patients received either second-line chemotherapy (gemcitabine and/or vinorelbine) or ICI therapy (pembrolizumab or nivolumab ± ipilimumab). The primary outcome was OS, defined as the time from second-line therapy initiation to death or end of the observation period. We used Kaplan-Meier methods and Cox proportional hazards modeling with adjustment for relevant patient demographic and clinical variables to compare OS between the two second-line treatment groups.

Results: Of the 176 patients with MPM, the median age was 75 years (IQR: 69-79.5 years), and most were white (77%), male (74%), and had epithelioid histology (67%). Thirty-five percent (61) received second-line chemotherapy and 65% (115) ICI therapy (80 pembrolizumab, 31 nivolumab, and 4 nivolumab + ipilimumab). Treatment with ICI was associated with significantly longer median OS compared to chemotherapy (8.7 vs 5.0 months, p=0.001; adjusted hazard ratio: 0.52, 95% CI: 0.34-0.81). The estimated 12-month OS probability was 36.7% (95% CI: 27.6%-45.8%) and 15.6% (95% CI: 7.7%-26.1%) in the ICI and chemotherapy groups, respectively.

Conclusion: In this "real-world" population of patients with MPM, treatment with ICI was associated with improved OS outcomes compared to chemotherapy in the second-line setting, in contrast with a recent clinical trial. Our findings suggest that ICI may benefit patients with advanced MPM and progression after initial platinum-based chemotherapy.

Copyright © 2021 Elsevier B.V. All rights reserved.

In plain English

This retrospective cohort study compared second-line treatments for malignant pleural mesothelioma. The authors used 2015 to 2019 records from the nationwide Flatiron Health database for 176 adults first treated with platinum-based chemotherapy. Of these, 61 then received chemotherapy (gemcitabine and/or vinorelbine) and 115 received immune checkpoint inhibitors (80 pembrolizumab, 31 nivolumab, 4 nivolumab plus ipilimumab). Median overall survival from the start of second-line treatment was 5.0 months (95% CI 4.0 to 6.4) with chemotherapy and 8.7 months (95% CI 7.7 to 10.9) with immune checkpoint inhibitors. Estimated 12-month survival was 15.6% (95% CI 7.7% to 26.1%) and 36.7% (95% CI 27.6% to 45.8%), respectively. After adjustment for age, sex, race, tumor subtype and other factors, immune checkpoint inhibitor treatment was associated with improved overall survival (adjusted hazard ratio 0.52, 95% CI 0.34 to 0.81). The authors concluded that their results suggest a possible benefit of second-line immune checkpoint inhibitors over chemotherapy in routine care. They cautioned that patients may have been chosen for immunotherapy because of a better outlook. They said the study was too small to assess differences by tumor subtype.

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: Retrospective, multicenter cohort study (comparative effectiveness) using electronic health record-derived data
• Who was studied: 176 adults with malignant pleural mesothelioma in the nationwide Flatiron Health database, January 1, 2015 to December 31, 2019. All had received first-line platinum-based chemotherapy and at least two lines of systemic therapy. Median age was 75 years; 77% were white, 74% male, and 67% had epithelioid histology.
• Exposure: Second-line treatment, not asbestos exposure. Second-line therapies were grouped as chemotherapy (gemcitabine and/or vinorelbine) or immune checkpoint inhibitor therapy (pembrolizumab or nivolumab with or without ipilimumab).
• Main results:
  • Chemotherapy group: 61 patients (35%), of whom 48 received gemcitabine, 11 vinorelbine, and 2 gemcitabine plus vinorelbine.
  • Immune checkpoint inhibitor group: 115 patients (65%), of whom 80 received pembrolizumab, 31 nivolumab, and 4 nivolumab plus ipilimumab.
  • Deaths: 91.8% (56/61) of patients receiving chemotherapy died, compared with 79.1% (91/115) of those receiving immune checkpoint inhibitors (P=0.031).
  • Median overall survival was 5.0 months (95% CI 4.0 to 6.4) in the chemotherapy group and 8.7 months (95% CI 7.7 to 10.9) in the immune checkpoint inhibitor group (P=0.001).
  • Estimated 12-month overall survival was 15.6% (95% CI 7.7% to 26.1%) in the chemotherapy group and 36.7% (95% CI 27.6% to 45.8%) in the immune checkpoint inhibitor group.
  • Compared with chemotherapy, second-line immune checkpoint inhibitor treatment was associated with improved overall survival (adjusted hazard ratio 0.52, 95% CI 0.34 to 0.81).
  • Compared with chemotherapy, adjusted hazard ratios were 0.49 (95% CI 0.31 to 0.77) for pembrolizumab and 0.63 (95% CI 0.37 to 1.07) for nivolumab with or without ipilimumab. For pembrolizumab versus nivolumab with or without ipilimumab, the adjusted hazard ratio was 0.81 (95% CI 0.51 to 1.28), which the authors reported as no difference.
  • In sensitivity analyses, immune checkpoint inhibitor treatment continued to be associated with improved overall survival. The adjusted hazard ratio was 0.50 (95% CI 0.29 to 0.85) among patients with baseline ECOG performance status 0 to 1, and 0.51 (95% CI 0.31 to 0.84) among patients not given first-line bevacizumab.
  • An interaction between second-line therapy and histologic subtype was not statistically significant (P=0.804).
• The authors' conclusion: The authors concluded that their results suggest a possible benefit of second-line immune checkpoint inhibitors over chemotherapy among patients receiving routine clinical care. They said further investigation is needed, including on whether outcomes vary by histologic subtype.
• Limitations the authors state:
  • Possible confounding by indication: patients may have been chosen for immune checkpoint inhibitors because of favorable characteristics that predicted a better prognosis.
  • Patients in the immune checkpoint inhibitor group were treated more recently and more often received first-line bevacizumab.
  • The study was underpowered to assess whether the benefit differed by histologic subtype.

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: checkpoint inhibitors, Chemotherapy, Pleural Mesothelioma, Overall Survival, Cohort Study, Systemic Therapy, Gemcitabine, Vinorelbine.

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