Pan‐Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System

ABSTRACT Background The cumulative, health system‐wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real‐world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system‐wide su...

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Main Authors: Sean R. Miller, Matthew Schipper, Lars G. Fritsche, Ralph Jiang, Garth Strohbehn, Erkin Ötleş, Benjamin H. McMahon, Silvia Crivelli, Rafael Zamora‐Resendiz, Nithya Ramnath, Shinjae Yoo, Xin Dai, Kamya Sankar, Donna M. Edwards, Steven G. Allen, Michael D. Green, Alex K. Bryant
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70379
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author Sean R. Miller
Matthew Schipper
Lars G. Fritsche
Ralph Jiang
Garth Strohbehn
Erkin Ötleş
Benjamin H. McMahon
Silvia Crivelli
Rafael Zamora‐Resendiz
Nithya Ramnath
Shinjae Yoo
Xin Dai
Kamya Sankar
Donna M. Edwards
Steven G. Allen
Michael D. Green
Alex K. Bryant
author_facet Sean R. Miller
Matthew Schipper
Lars G. Fritsche
Ralph Jiang
Garth Strohbehn
Erkin Ötleş
Benjamin H. McMahon
Silvia Crivelli
Rafael Zamora‐Resendiz
Nithya Ramnath
Shinjae Yoo
Xin Dai
Kamya Sankar
Donna M. Edwards
Steven G. Allen
Michael D. Green
Alex K. Bryant
author_sort Sean R. Miller
collection DOAJ
description ABSTRACT Background The cumulative, health system‐wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real‐world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system‐wide survival impact of ICIs. Methods We identified all patients receiving PD‐1/PD‐L1 or CTLA‐4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non‐ICI systemic therapy in the years before ICI approval (historical control). ICI and historical control cohorts were matched on multiple cancer‐related prognostic factors, comorbidities, and demographics. The effect of ICI on overall survival was quantified with Cox regression incorporating matching weights. Cumulative life‐years gained system‐wide were calculated from the difference in adjusted 5‐year restricted mean survival times. Results There were 27,322 patients in the ICI cohort and 69,801 patients in the historical control cohort. Among ICI patients, the most common cancer types were NSCLC (46%) and melanoma (10%). ICI demonstrated a large OS benefit in most cancer types with heterogeneity across cancer types (NSCLC: adjusted HR [aHR] 0.56, 95% confidence interval [CI] 0.54–0.58, p < 0.001; urothelial: aHR 0.91, 95% CI 0.83–1.01, p = 0.066). The relative benefit of ICI was stable across patient age, comorbidity, and self‐reported race subgroups. Across VHA, 15,859 life‐years gained were attributable to ICI within 5‐years of treatment, with NSCLC contributing the most life‐years gained. Conclusion We demonstrated substantial increase in survival due to ICIs across a national health system, including in patient subgroups poorly represented on clinical trials.
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spelling doaj-art-9a3b346a3ce341aea34bb04656fb9eec2025-08-20T02:14:39ZengWileyCancer Medicine2045-76342024-11-011321n/an/a10.1002/cam4.70379Pan‐Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare SystemSean R. Miller0Matthew Schipper1Lars G. Fritsche2Ralph Jiang3Garth Strohbehn4Erkin Ötleş5Benjamin H. McMahon6Silvia Crivelli7Rafael Zamora‐Resendiz8Nithya Ramnath9Shinjae Yoo10Xin Dai11Kamya Sankar12Donna M. Edwards13Steven G. Allen14Michael D. Green15Alex K. Bryant16Department of Radiation Oncology Veterans Affairs Ann Arbor Healthcare System Ann Arbor Michigan USADepartment of Biostatistics University of Michigan Ann Arbor Michigan USADepartment of Biostatistics University of Michigan Ann Arbor Michigan USADepartment of Biostatistics University of Michigan Ann Arbor Michigan USAVeterans Affairs Center for Clinical Management Research Ann Arbor Michigan USAMedical Scientist Training Program University of Michigan Medical School Ann Arbor Michigan USATheoretical Biology and Biophysics Los Alamos National Laboratory Los Alamos New Mexico USAApplied Mathematics and Computational Research Division Lawrence Berkeley National Laboratory Berkeley California USAApplied Mathematics and Computational Research Division Lawrence Berkeley National Laboratory Berkeley California USADivision of Medical Oncology, Department of Medicine Veterans Affairs Ann Arbor Healthcare System Ann Arbor Michigan USAComputational Science Initiative Brookhaven National Laboratory Upton New York USAComputational Science Initiative Brookhaven National Laboratory Upton New York USADivision of Medical Oncology, Department of Medicine Samuel Oschin Comprehensive Cancer Institute, Cedars‐Sinai Medical Center Los Angeles California USADepartment of Radiation Oncology Veterans Affairs Ann Arbor Healthcare System Ann Arbor Michigan USADepartment of Radiation Oncology Veterans Affairs Ann Arbor Healthcare System Ann Arbor Michigan USADepartment of Radiation Oncology Veterans Affairs Ann Arbor Healthcare System Ann Arbor Michigan USADepartment of Radiation Oncology Veterans Affairs Ann Arbor Healthcare System Ann Arbor Michigan USAABSTRACT Background The cumulative, health system‐wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real‐world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system‐wide survival impact of ICIs. Methods We identified all patients receiving PD‐1/PD‐L1 or CTLA‐4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non‐ICI systemic therapy in the years before ICI approval (historical control). ICI and historical control cohorts were matched on multiple cancer‐related prognostic factors, comorbidities, and demographics. The effect of ICI on overall survival was quantified with Cox regression incorporating matching weights. Cumulative life‐years gained system‐wide were calculated from the difference in adjusted 5‐year restricted mean survival times. Results There were 27,322 patients in the ICI cohort and 69,801 patients in the historical control cohort. Among ICI patients, the most common cancer types were NSCLC (46%) and melanoma (10%). ICI demonstrated a large OS benefit in most cancer types with heterogeneity across cancer types (NSCLC: adjusted HR [aHR] 0.56, 95% confidence interval [CI] 0.54–0.58, p < 0.001; urothelial: aHR 0.91, 95% CI 0.83–1.01, p = 0.066). The relative benefit of ICI was stable across patient age, comorbidity, and self‐reported race subgroups. Across VHA, 15,859 life‐years gained were attributable to ICI within 5‐years of treatment, with NSCLC contributing the most life‐years gained. Conclusion We demonstrated substantial increase in survival due to ICIs across a national health system, including in patient subgroups poorly represented on clinical trials.https://doi.org/10.1002/cam4.70379check point controlclinical cancer researchclinical observationsimmune checkpoint inhibitors
spellingShingle Sean R. Miller
Matthew Schipper
Lars G. Fritsche
Ralph Jiang
Garth Strohbehn
Erkin Ötleş
Benjamin H. McMahon
Silvia Crivelli
Rafael Zamora‐Resendiz
Nithya Ramnath
Shinjae Yoo
Xin Dai
Kamya Sankar
Donna M. Edwards
Steven G. Allen
Michael D. Green
Alex K. Bryant
Pan‐Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System
Cancer Medicine
check point control
clinical cancer research
clinical observations
immune checkpoint inhibitors
title Pan‐Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System
title_full Pan‐Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System
title_fullStr Pan‐Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System
title_full_unstemmed Pan‐Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System
title_short Pan‐Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System
title_sort pan cancer survival impact of immune checkpoint inhibitors in a national healthcare system
topic check point control
clinical cancer research
clinical observations
immune checkpoint inhibitors
url https://doi.org/10.1002/cam4.70379
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