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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| Format: | Article |
| Language: | English |
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Wiley
2024-11-01
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| 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. |
| format | Article |
| id | doaj-art-9a3b346a3ce341aea34bb04656fb9eec |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| 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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