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. 2024 Nov;13(21):e70379.
doi: 10.1002/cam4.70379.

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

Sean R Miller  1   2 , Matthew Schipper  3 , Lars G Fritsche  3   4 , Ralph Jiang  3 , Garth Strohbehn  5   6   7   8 , Erkin Ötleş  9 , Benjamin H McMahon  10 , Silvia Crivelli  11 , Rafael Zamora-Resendiz  11 , Nithya Ramnath  6   7 , Shinjae Yoo  12 , Xin Dai  12 , Kamya Sankar  13 , Donna M Edwards  1   2 , Steven G Allen  1   2 , Michael D Green  1   2 , Alex K Bryant  1   2
Affiliations

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

Sean R Miller et al. Cancer Med. 2024 Nov.

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.

Keywords: check point control; clinical cancer research; clinical observations; immune checkpoint inhibitors.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
ICI utilization in the national VA system. (A) Proportion of patients receiving ICI, all stages at diagnosis. (B) Proportion of patients receiving ICI, metastatic at diagnosis. (C) Absolute number of patients receiving ICI, all stages at diagnosis. (D) Absolute number of patients receiving ICI, metastatic at diagnosis. ICI: Immune checkpoint inhibitors; SCC: Squamous cell carcinoma; NSCLC: Non‐small‐cell lung cancer; SCLC: Small‐cell lung cancer.
FIGURE 2
FIGURE 2
Overall survival by cancer type. Weighted Kaplan–Meier overall survival curves for ICI (blue) and historical control (red) cohorts, by cancer type (panels A‐I). Dotted lines indicated median survival times. ICI, immune checkpoint inhibitors; SCC, squamous cell carcinoma; NSCLC, non‐small‐cell lung cancer; SCLC, small‐cell lung cancer.
FIGURE 3
FIGURE 3
Life‐years gained across the Veterans Affairs system attributable to immune checkpoint inhibitors. (A) Cumulative absolute expected life‐years gained attributable to ICI among patients treated from 2012 to 2022, calculated over a 5‐year time horizon after treatment. (B) Percentage of life‐years gained attributable to each cancer type.
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