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

Miller SR, Schipper M, Fritsche LG, Jiang R, Strohbehn G, Ötles E, McMahon BH, Crivelli S, Zamora-Resendiz R, Ramnath N, Yoo S, Dai X, Sankar K, Edwards DM, Allen SG, Green MD, Bryant AK. Pan-Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System. Cancer medicine. 2024 Nov 1; 13(21):e70379, DOI: 10.1002/cam4.70379.

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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.