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

Abstract

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. 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. 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. We demonstrated substantial increase in survival due to ICIs across a national health system, including in patient subgroups poorly represented on clinical trials.