Immune Checkpoint Inhibitor Uptake in Real-World Patients With Malignant Pleural Mesothelioma

Our plain-English summary of Immune Checkpoint Inhibitor Uptake in Real-World Patients With Malignant Pleural Mesothelioma, by R.Y. Kim, N. Mitra, S.J. Bagley, et al (JTO Clinical and Research Reports, 2021).

The study

• Authors: R.Y. Kim, N. Mitra, S.J. Bagley, M.E. Marmarelis, A.R. Haas, K.A. Rendle, A. Vachani
• Journal: JTO Clinical and Research Reports
• Published: 2021;2(6):100188
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Since the July 2017 National Comprehensive Cancer Network (NCCN) malignant pleural mesothelioma (MPM) guideline revision recommended second-line immune checkpoint inhibitors (ICIs), studies have suggested a greater response to ICI among patients with nonepithelioid MPM. Nevertheless, little is known regarding adoption of ICI in routine practice and if uptake differs by histologic subtype. Our objectives were to evaluate the real-world uptake of second-line ICI among patients with MPM and to reveal its association with histologic subtype.

Methods: This was a multicenter, retrospective cohort study of real-world patients with MPM receiving at least two lines of systemic therapy between 2011 and 2019. We found the uptake of second-line ICI over time and evaluated the association between histologic subtype and ICI use, adjusting for relevant patient demographic and clinical factors.

Results: Among the 426 patients with MPM in our cohort, 310 had epithelioid and 116 nonepithelioid histologic subtype. The median age was 73 years (interquartile range: 67-78). Overall, 144 patients (33.8%) received second-line ICI and 282 (66.2%) traditional chemotherapy. ICI uptake began in early 2015 before the NCCN guideline revision and increased rapidly to 2019. After the 2017 NCCN guideline revision, patients with nonepithelioid MPM histologic subtypes had more than 3 times the odds of receiving second-line ICI (OR = 3.26; 95% confidence interval: 1.41-7.54).

Conclusions: Among real-world patients with MPM, second-line ICI uptake began over two years before the 2017 NCCN guideline recommendations and was associated with nonepithelioid histologic subtype after contemporary studies suggested increased clinical benefit in this population, reflecting prompt integration of scientific discovery into clinical practice.

© 2021 The Authors.

In plain English

This retrospective cohort study used deidentified electronic health records from the Flatiron Health database, covering 133 U.S. cancer clinics from 2011 to 2019. It studied treatment choice, not asbestos. It included 426 adults with malignant pleural mesothelioma who had guideline-recommended first-line chemotherapy and then a second line of treatment. Of these, 310 had the epithelioid subtype and 116 the nonepithelioid (sarcomatoid or biphasic) subtype. Asbestos exposure was recorded as present for 285 patients (66.9%). Overall, 144 patients (33.8%) received second-line immune checkpoint inhibitors (pembrolizumab, or nivolumab with or without ipilimumab), and 282 (66.2%) received traditional chemotherapy. Use began in 2015, before the July 2017 guideline revision. By that revision, the cumulative share was 27.4% (45 of 164), and it rose to 45.3% (144 of 318) by December 2019. After the revision, nonepithelioid patients had higher odds of receiving these drugs (adjusted odds ratio 3.26, 95% confidence interval 1.41 to 7.54). Before it, the adjusted odds ratio was 1.12 (0.52 to 2.44). The authors concluded that oncologists were early adopters. They noted possible unmeasured confounding and did not study survival.

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 deidentified electronic health record data (Flatiron Health database)
• Who was studied: 426 adults with malignant pleural mesothelioma treated at U.S. cancer clinics in the Flatiron Health database (133 clinics in the source data set), 2011 to 2019. All received NCCN guideline-concordant first-line chemotherapy and a guideline-concordant second-line therapy. 310 (72.8%) were epithelioid and 116 (27.2%) nonepithelioid (48 sarcomatoid, 68 biphasic). Median age was 73.
• Exposure: Not an asbestos exposure study. The factor studied was histologic subtype (epithelioid vs nonepithelioid). The outcome was receipt of second-line immune checkpoint inhibitors (pembrolizumab or nivolumab with or without ipilimumab) versus traditional chemotherapy, before and after the July 7, 2017 NCCN guideline revision.
• Main results:
  • Of all 426 patients, 144 (33.8%) received second-line immune checkpoint inhibitors and 282 (66.2%) traditional chemotherapy.
  • Cumulative uptake among eligible patients reached 27.4% (45 of 164) before the July 2017 guideline revision.
  • Cumulative uptake among eligible patients reached 45.3% (144 of 318) by December 2019.
  • After the guideline change, cumulative uptake by December 2019 was 55.8% in nonepithelioid versus 41.4% in epithelioid patients.
  • After the guideline revision, nonepithelioid patients had higher odds of receiving second-line immune checkpoint inhibitors than epithelioid patients: unadjusted OR 2.50 (95% CI 1.15 to 5.41).
  • After the guideline revision, the adjusted OR for nonepithelioid versus epithelioid patients was 3.26 (95% CI 1.41 to 7.54).
  • Before the guideline revision, the adjusted OR for nonepithelioid versus epithelioid patients was 1.12 (95% CI 0.52 to 2.44), p = 0.767.
  • Asbestos exposure, recorded descriptively only, was 'Yes' for 285 (66.9%) of the 426 patients, 'No' for 75 (17.6%), and missing for 66 (15.5%).
  • Sensitivity analyses did not substantially change the findings.
• The authors' conclusion: The authors concluded that oncologists treating malignant pleural mesothelioma were early adopters of immune checkpoint inhibitors. They concluded that oncologists may have based their choice on contemporary data suggesting greater benefit in nonepithelioid tumors.
• Limitations the authors state:
  • Retrospective, nonrandomized design means unmeasured confounding is possible.
  • PD-L1 expression data were largely missing, so its role in treatment choice could not be evaluated.
  • Race, ECOG performance status and insurance data were missing for some patients and were handled with multiple imputation.
  • Performance status at the start of second-line therapy was unavailable for most patients, so baseline status was used.
  • Clinical outcomes such as overall survival were not evaluated.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Pleural Mesothelioma, Histological Subtype, Cohort Study, Systemic Therapy, Epithelioid, Chemotherapy, confidence interval.

Related studies

• Immune-Checkpoint Inhibitors for Malignant Pleural Mesothelioma: A French, Multicenter, Retrospective Real-World Study — J.B. Assié, F. Crépin, et al. (2022)
• Comparative effectiveness of second-line immune checkpoint inhibitor therapy versus chemotherapy for malignant pleural mesothelioma — R.Y. Kim, Y. Li, et al. (2021)
• Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors — A. Vogrig, M. Fouret, et al. (2019)
• Immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): Approaches on special subgroups and unresolved burning questions — J. Remon, N. Vilariño, et al. (2018)
• Immune checkpoint inhibitor associated reactivation of primary membranous nephropathy responsive to rituximab — J.S. Lin, D.Y. Wang, et al. (2020)
• Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma — K. Hotta, N. Fujimoto (2020)

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