Kim Yeijin, Liu Yan, Suh Hae Sun, Park Chanhyun
College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
Health Outcomes Division, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
Cancer Control. 2025 Jan-Dec;32:10732748251380932. doi: 10.1177/10732748251380932. Epub 2025 Oct 3.
IntroductionDespite improved outcomes with PD-1 inhibitors (PD-1i) in advanced non-small cell lung cancer (NSCLC), the determinants of cancer-, cardiovascular disease (CVD)-, and other-cause mortality remain poorly characterized in older adults. This study applies competing-risks methods to estimate cause-specific mortality and to identify predictors for each cause in this population.MethodsA retrospective cohort study was conducted using the 2014-2019 SEER-Medicare linked database, including patients aged 65 years or older with advanced NSCLC who received PD-1i (nivolumab or pembrolizumab). Mortality outcomes included deaths from CVD, NSCLC, other cancers, and other diseases. Predictors included treatment-related factors (e.g., PD-1i type), demographic factors (e.g., age, sex), socioeconomic status (e.g., Medicaid dual eligibility), cancer-related factors (e.g., NSCLC stage), and comorbidities (e.g., congestive heart failure [CHF]). Competing risk analyses were performed using the Fine-Gray model, with cause-specific Cox models for sensitivity analyses.ResultsAmong 5076 patients, 68.36% received nivolumab and 31.64% received pembrolizumab. Of 3746 deaths, most were from NSCLC (85.34%), while 2.80% were from CVD. No significant difference in CVD mortality risk was observed between the two PD-1i (sub-distribution HR [sHR] = 1.08; 95% CI: 0.63-1.84), but NSCLC mortality was associated with a lower risk in the pembrolizumab group (sHR = 0.67; 95% CI: 0.60-0.74) compared to the nivolumab group. A history of CHF (sHR = 2.10; 95% CI: 1.37-3.21) and Medicaid dual eligibility (sHR = 2.70 vs private insurance; 95% CI: 1.28-5.56) were associated with increased CVD mortality. NSCLC mortality was higher in Stage IV/distant than in Stage IIIB/regional (sHR = 1.24; 95% CI: 1.13-1.35) and males (sHR = 1.11; 95% CI: 1.03-1.20).ConclusionsThese results highlight the potential value of integrated cardio-oncology models and strategies addressing socioeconomic inequities among older adults receiving PD-1i. However, conclusions should be tempered by the SEER-Medicare data structure, including lack of biomarker information and restricted applicability to younger or non-Medicare populations.
引言
尽管在晚期非小细胞肺癌（NSCLC）中，程序性死亡受体1抑制剂（PD-1i）改善了治疗效果，但在老年患者中，癌症、心血管疾病（CVD）和其他原因导致的死亡率的决定因素仍未得到充分描述。本研究应用竞争风险方法来估计特定原因的死亡率，并确定该人群中每种原因的预测因素。
方法
使用2014 - 2019年SEER - Medicare链接数据库进行了一项回顾性队列研究，纳入年龄在65岁及以上、接受PD-1i（纳武利尤单抗或帕博利珠单抗）治疗的晚期NSCLC患者。死亡结局包括死于CVD、NSCLC、其他癌症和其他疾病。预测因素包括治疗相关因素（如PD-1i类型）、人口统计学因素（如年龄、性别）、社会经济状况（如医疗补助双重资格）、癌症相关因素（如NSCLC分期）和合并症（如充血性心力衰竭[CHF]）。使用Fine-Gray模型进行竞争风险分析，并使用特定原因的Cox模型进行敏感性分析。
结果
在5076例患者中，68.36%接受了纳武利尤单抗治疗，31.64%接受了帕博利珠单抗治疗。在3746例死亡病例中，大多数死于NSCLC（85.34%），而2.80%死于CVD。两种PD-1i之间未观察到CVD死亡风险的显著差异（亚分布风险比[sHR]=1.08；95%置信区间：0.63 - 1.84），但与纳武利尤单抗组相比，帕博利珠单抗组的NSCLC死亡率风险较低（sHR = 0.67；95%置信区间：0.60 - 0.74）。CHF病史（sHR = 2.10；95%置信区间：1.37 - 3.21）和医疗补助双重资格（与私人保险相比，sHR = 2.70；95%置信区间：1.28 - 5.56）与CVD死亡率增加相关。IV期/远处转移患者的NSCLC死亡率高于IIIB期/局部区域患者（sHR = 1.24；95%置信区间：1.13 - 1.35），男性患者的NSCLC死亡率也较高（sHR = 1.11；95%置信区间：1.03 - 1.20）。
结论
这些结果凸显了综合心脏肿瘤学模型和策略在解决接受PD-1i治疗的老年患者社会经济不平等方面的潜在价值。然而，这些结论应结合SEER - Medicare数据结构进行考量，包括缺乏生物标志物信息以及对年轻或非医疗保险人群适用性有限的问题。
