McManus Hannah D, Long Jessica B, Westvold Sarah J, Leapman Michael S, Hurwitz Michael E, Mitchell Aaron P, Pollack Craig Evan, Gross Cary P, Dinan Michaela A
Department of Medicine, Duke University School of Medicine, Durham, NC.
Yale Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT; Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
Clin Genitourin Cancer. 2025 Jun;23(3):102330. doi: 10.1016/j.clgc.2025.102330. Epub 2025 Mar 15.
Immune checkpoint inhibitors (ICI) were approved by the Food and Drug Administration (FDA) for patients with metastatic renal cell carcinoma (mRCC) in the second- line setting in 2015 and the first-line (1L) in 2018. Little is known about 1 L ICI use in the off-label (before FDA indication-specific approval) and postapproval settings.
We retrospectively analyzed off-label and post-FDA-approval 1 L ICI receipt in a cohort of Medicare beneficiaries ≥66 years old diagnosed with mRCC from 2015 to 2019. Off-label and postapproval 1 L ICI were defined as before or on/after 4/16/2018 (1L ipilimumab/nivolumab approval). Associations between demographic characteristics and 1 L ICI receipt in the off-label and postapproval periods were examined using multivariable logistic regression.
We identified 23,469 patients, of which 368 (2.4%) off-label and 1,663 (21%) postapproval received 1 L ICI. In the off-label period, patients with co-morbid conditions were more likely to receive 1 L ICI compared to patients with no co-morbidities (3+ conditions, OR = 2.00; 95% CL, 1.31-3.05). In the postapproval period, older patients were less likely to receive 1 L ICI (81+ vs. 66-70, OR = 0.60; 95% CL, 0.52-0.69), and patients who were frail were less likely to receive 1 L ICI (OR = 0.77; 95% CL, 0.69-0.87). There were not significant differences in 1 L ICI receipt based on race/ethnicity.
Older patients and patients with more comorbidities were more likely to receive 1 L ICI off-label, but these differences did not persist after FDA approval. After 1 L ipilimumab/nivolumab approval, patients receiving 1 L ICI were more likely younger, healthy, and receiving dual-ICI regimens.
免疫检查点抑制剂（ICI）于2015年被美国食品药品监督管理局（FDA）批准用于二线转移性肾细胞癌（mRCC）患者，并于2018年批准用于一线（1L）治疗。对于在标签外（在FDA特定适应症批准之前）和批准后使用1L ICI的情况，人们了解甚少。
我们回顾性分析了2015年至2019年诊断为mRCC的≥66岁医疗保险受益人群中标签外和FDA批准后接受1L ICI治疗的情况。标签外和批准后1L ICI被定义为在2018年4月16日之前或之后（1L伊匹木单抗/纳武单抗批准）。使用多变量逻辑回归分析人口统计学特征与标签外和批准后时期接受1L ICI治疗之间的关联。
我们识别出23469例患者，其中368例（2.4%）在标签外接受治疗，1663例（21%）在批准后接受1L ICI治疗。在标签外时期，与无合并症的患者相比，有合并症的患者更有可能接受1L ICI治疗（3种及以上合并症，OR = 2.00；95%置信区间，1.31 - 3.05）。在批准后时期，老年患者接受1L ICI治疗的可能性较小（81岁及以上与66 - 70岁相比，OR = 0.60；95%置信区间，0.52 - 0.69），体弱患者接受1L ICI治疗的可能性较小（OR = 0.77；95%置信区间，0.69 - 0.87）。基于种族/民族，接受1L ICI治疗没有显著差异。
老年患者和合并症较多的患者更有可能在标签外接受1L ICI治疗，但这些差异在FDA批准后并未持续存在。在1L伊匹木单抗/纳武单抗批准后，接受1L ICI治疗的患者更可能是年轻、健康且接受双联ICI方案的患者。
