Department of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, USA.
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Cancer Med. 2024 Nov;13(21):e70379. doi: 10.1002/cam4.70379.
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.
免疫检查点抑制剂（ICIs）的累积、全系统生存获益尚不清楚，特别是在预期寿命有限的真实世界患者以及临床试验代表性不足的亚组中。我们旨在确定 ICI 对全系统生存的影响。
我们在国家退伍军人健康管理局（VHA）系统中确定了 2010 年至 2023 年期间接受 PD-1/PD-L1 或 CTLA-4 抑制剂治疗的所有患者（ICI 队列），以及在 ICI 批准前几年接受非 ICI 全身治疗的所有患者（历史对照组）。ICI 和历史对照组在多个与癌症相关的预后因素、合并症和人口统计学方面进行了匹配。通过纳入匹配权重的 Cox 回归来量化 ICI 对总生存期的影响。通过调整后 5 年限制平均生存时间的差异计算全系统获得的累计寿命年数。
ICI 队列中有 27322 例患者，历史对照组中有 69801 例患者。在 ICI 患者中，最常见的癌症类型是 NSCLC（46%）和黑色素瘤（10%）。ICI 在大多数癌症类型中表现出较大的 OS 获益，但癌症类型之间存在异质性（NSCLC：调整后的 HR[aHR]0.56，95%置信区间[CI]0.54-0.58，p<0.001；尿路上皮癌：aHR 0.91，95%CI 0.83-1.01，p=0.066）。ICI 的相对获益在患者年龄、合并症和自我报告的种族亚组中保持稳定。在 VHA 中，治疗后 5 年内，ICI 导致 15859 个寿命年的获益，其中 NSCLC 贡献了最多的寿命年获益。
我们在全国卫生系统中证明了 ICI 带来的生存显著提高，包括在临床试验代表性不足的患者亚组中。
