A Real-World Analysis of the Use of Systemic Therapy in Malignant Pleural Mesothelioma and the Differential Impacts on Overall Survival by Practice Pattern

Our plain-English summary of A Real-World Analysis of the Use of Systemic Therapy in Malignant Pleural Mesothelioma and the Differential Impacts on Overall Survival by Practice Pattern, by K. Kerrigan, Y. Jo, J. Chipman, et al (JTO Clinical and Research Reports, 2022).

The study

• Authors: K. Kerrigan, Y. Jo, J. Chipman, B. Haaland, S. Puri, W. Akerley, S. Patel
• Journal: JTO Clinical and Research Reports
• Published: 2022;3(3):100280
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is an aggressive malignancy that affects older adults with frequent comorbidities, making real-world treatment decisions challenging. This study compares the overall survival (OS) of patients with MPM by physician's choice of first-line (1L) platinum chemotherapy (PC), second-line (2L) immunotherapy versus chemotherapy, and by receipt of maintenance therapy (MT).

Methods: The study included patients diagnosed with advanced MPM in the Flatiron Health electronic health record-derived database who initiated PC with pemetrexed in the 1L setting between 2011 and 2019. Patients in the 2L therapy analysis received single-agent chemotherapy versus immunotherapy after the progression of disease from our 1L cohort. Patients in the MT cohort were identified on the basis of continued receipt of pemetrexed with or without bevacizumab after dropping PC at prespecified intervals. The OS of patients by choice of 1L PC, 2L immunotherapy versus chemotherapy, and receipt of MT was summarized by means of Kaplan-Meier survival estimates and compared in the context of propensity score matching weighted analyses.

Results: In propensity score matching weighting analysis from 2065 patients with MPM, there was no evidence of an OS difference by choice of 1L PC (hazard ratio [HR] = 1.08, 95% confidence interval [CI]: 0.89-1.31, p = 0.43), suggestive evidence of an OS difference by choice of 2L immunotherapy versus chemotherapy (HR = 0.68, 95% CI: 0.42-1.08; p = 0.10), and no evidence of an OS difference by receipt of MT (HR = 0.92, 95% CI: 0.72-1.16, p = 0.46).

Conclusions: Using real-world, propensity score-matched weighted analysis of MPM, we found there was no difference in OS by choice of 1L PC, 2L immunotherapy or chemotherapy, or by receipt of MT.

© 2022 The Authors.

In plain English

This retrospective study used U.S. Flatiron Health treatment records for patients diagnosed with malignant pleural mesothelioma from January 2011 to July 2019. It examined treatment choices and survival, not asbestos as a cause; asbestos exposure history was recorded and was one of the subgroups tested for differing treatment effects. Propensity score weighting was used to balance treatment groups. Among 787 first-line patients, survival did not differ statistically significantly between cisplatin (323) and carboplatin (464): hazard ratio 1.08 (95% CI 0.89–1.31). Among 192 second-line patients, median survival from the start of that treatment was 8.05 months (95% CI 7.13–11.43) with immunotherapy (88) and 4.90 months (95% CI 3.78–6.08) with single-agent chemotherapy (104). The weighted hazard ratio, 0.68 (95% CI 0.42–1.08), was not strong evidence of benefit. In the sarcomatoid subgroup it was 0.21 (95% CI 0.06–0.71). Comparing 167 patients who received maintenance therapy with 315 who did not, the hazard ratio was 0.92 (95% CI 0.72–1.16). The authors concluded there were no statistically significant survival differences by these treatment choices. They noted incomplete records and possible unmeasured confounding.

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 real-world analysis of electronic health record data, comparing treatment groups using propensity score matching weights and Cox proportional hazards models
• Who was studied: U.S. patients diagnosed with malignant pleural mesothelioma between January 2011 and July 2019 and treated with first-line carboplatin or cisplatin plus pemetrexed, with or without bevacizumab. Data came from about 280 U.S. cancer clinics. The first-line cohort had 787 patients, the second-line cohort 192 and the maintenance cohort 482.
• Exposure: Treatments compared: first-line cisplatin versus carboplatin, each given with pemetrexed; second-line immunotherapy versus single-agent chemotherapy; and maintenance pemetrexed with or without bevacizumab versus no maintenance. Asbestos exposure was collected as a baseline characteristic and used as one of the subgroups tested for differences in treatment effect. It was not studied as a cause of mesothelioma.
• Main results:
  • Asbestos exposure was documented as 'Yes' in 315 of 464 carboplatin-treated patients (67.9%) and in 221 of 323 cisplatin-treated patients (68.4%) in the first-line cohort.
  • Ever-exposure to asbestos (yes/no) was one of the subgroups used to test whether treatment effects on survival differed (effect modification).
  • First-line cohort, after weighting: median overall survival was 12.1 months (95% CI 10.4–14.3) with carboplatin and 11.9 months (95% CI 10.5–13.8) with cisplatin.
  • First-line cohort: the hazard ratio for cisplatin compared with carboplatin was 1.08 (95% CI 0.89–1.31), p = 0.43. The authors judged this insufficient evidence of a survival difference.
  • Second-line cohort (192 patients): median overall survival from the start of second-line therapy was 4.90 months (95% CI 3.78–6.08) with single-agent chemotherapy (104 patients) and 8.05 months (95% CI 7.13–11.43) with immunotherapy (88 patients).
  • Second-line cohort, after weighting: the hazard ratio for immunotherapy versus chemotherapy was 0.68 (95% CI 0.42–1.08, p = 0.10). The authors described this as no strong evidence that immunotherapy improved survival. After further adjustment for diagnosis year and race-ethnicity, the hazard ratio was 0.79 (95% CI 0.45–1.40, p = 0.42).
  • In second-line patients with sarcomatoid histology, immunotherapy was associated with better outcomes than single-agent chemotherapy: hazard ratio 0.21 (95% CI 0.06–0.71, p = 0.01).
  • Maintenance cohort (482 patients: 167 who received maintenance therapy and 315 who did not): the hazard ratio was 0.92 (95% CI 0.72–1.16, p = 0.46). The authors judged this insufficient evidence that maintenance therapy was beneficial.
• The authors' conclusion: The authors concluded that they found no statistically significant differences in overall survival by choice of first-line platinum chemotherapy, second-line chemotherapy versus immunotherapy, or use of maintenance therapy.
• Limitations the authors state:
  • Real-world health record data may be incomplete, and there may be confounding by factors that were not measured.
  • The data are affected by shifting practice patterns, health record use, testing and time trends.
  • PD-L1 status was often missing or not tested, so no firm conclusions could be drawn about this biomarker.

Topics

Medical terms in this study, explained in our Lexicon: Systemic Therapy, Pleural Mesothelioma, Overall Survival, Chemotherapy, Immunotherapy, Pemetrexed (Alimta), Bevacizumab, Hazard Ratio.

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