Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Cancer Immunol Immunother. 2023 Nov;72(11):3581-3591. doi: 10.1007/s00262-023-03508-1. Epub 2023 Aug 4.
To determine the associated thromboembolism risk with adding immune checkpoint inhibitors (ICI) to platinum combination chemotherapy compared with platinum combination chemotherapy alone in patients with advanced non-small cell lung cancer.
This study identified 75,807 patients with advanced non-small cell lung cancer from the Japanese Diagnosis Procedure Combination database who started platinum combination chemotherapy between July 2010 and March 2021. The incidence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and all-cause mortality within 6 months after commencing platinum combination chemotherapy was compared between patients receiving chemotherapy with ICI (ICI group, n = 7,177) and without ICI (non-ICI group, n = 37,903). Survival time analysis was performed using the overlap weighting method with propensity scores to adjust for background factors. The subdistribution hazard ratio for developing thromboembolism was calculated using the Fine-Gray model with death as a competing risk. The hazard ratio for all-cause mortality was also calculated using the Cox proportional hazards model.
Overall, VTE and ATE occurred in 761 (1.0%) and 389 (0.51%) patients, respectively; mortality was 11.7%. Propensity score overlap weighting demonstrated that the subdistribution hazard ratio (95% confidence interval) for VTE and ATE in the ICI group was 1.27 (1.01-1.60) and 0.96 (0.67-1.36), respectively, compared with the non-ICI group. The mortality hazard ratio in the ICI group was 0.68 (0.62-0.74).
The addition of ICI to platinum combination therapy was associated with a higher risk of VTE compared with platinum combination therapy alone, while the risk of ATE might be comparable.
确定与单独使用铂类联合化疗相比,晚期非小细胞肺癌患者接受免疫检查点抑制剂(ICI)联合铂类联合化疗的血栓栓塞风险。
本研究从日本诊断程序组合数据库中确定了 75807 名 2010 年 7 月至 2021 年 3 月开始接受铂类联合化疗的晚期非小细胞肺癌患者。比较了接受化疗联合 ICI(ICI 组,n=7177)和未接受 ICI(非-ICI 组,n=37903)的患者在开始铂类联合化疗后 6 个月内静脉血栓栓塞症(VTE)、动脉血栓栓塞症(ATE)和全因死亡率的发生率。使用倾向评分重叠加权法对背景因素进行调整,对生存时间进行分析。使用 Fine-Gray 模型计算发生血栓栓塞的亚分布风险比,将死亡作为竞争风险。使用 Cox 比例风险模型计算全因死亡率的风险比。
总体而言,761 例(1.0%)和 389 例(0.51%)患者发生 VTE 和 ATE,死亡率为 11.7%。倾向评分重叠加权表明,ICI 组 VTE 和 ATE 的亚分布风险比(95%置信区间)分别为 1.27(1.01-1.60)和 0.96(0.67-1.36),而非-ICI 组。ICI 组的死亡率风险比为 0.68(0.62-0.74)。
与单独使用铂类联合化疗相比,ICI 联合铂类联合化疗与 VTE 风险增加相关,而 ATE 风险可能相当。