Shah Mohsin, Marmarelis Melina E, Mamtani Ronac, Hennessy Sean
Center for Real-world Effectiveness and Safety of Therapeutics (CREST), and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
Clin Lung Cancer. 2022 Dec;23(8):731-736. doi: 10.1016/j.cllc.2022.07.003. Epub 2022 Jul 22.
A prior study found that, among advanced non-small cell lung cancer (aNSCLC) patients with PD-L1 expression 50% to 100% receiving immunotherapy as monotherapy, PD-L1 expression ≥ 90% was associated with longer survival. We sought to replicate this finding using real-world data from community oncology practices across the US.
Retrospective cohort study of aNSCLC patients who initiated pembrolizumab monotherapy for first line and had a PD-L1 expression ≥ 50% using a nationwide, deidentified longitudinal electronic health record-derived real-world database. The exposure of interest was very high PD-L1 expression, which was defined as ≥ 90%, compared to high PD-L1 expression, defined as 50% to 89%. The primary outcome was overall survival, measured from initiation of pembrolizumab to date of death, with censoring at last healthcare encounter. Multiple imputation was used to impute missing covariates. Propensity score-based inverse probability weighting (IPW) was used to address confounding in Kaplan-Meier curves and Cox proportional hazard regression models.
The cohort included 1952 aNSCLC patients receiving first-line pembrolizumab monotherapy. Half of cohort members were female, median age was 73 years (interquartile range, 65-80), 71% had non-squamous histology, 94% had a history of smoking, and 46% had very high PD-L1 expression. Median overall survival in the propensity score-weighted sample was 15.84 months for very high PD-L1 expression and 12.72 months for high PD-L1 expression. Having a very high PD-L1 expression was associated with lower hazard of mortality (IPW hazard ratio 0.79, 95% CI 0.69-0.91).
In this large national US cohort, patients with very high PD-L1 expression (≥ 90%) aNSCLC receiving first-line pembrolizumab experienced better median survival than those with high PD-L1 expression (50% to 89%).
先前的一项研究发现,在接受免疫疗法单药治疗的程序性死亡受体配体1(PD-L1)表达为50%至100%的晚期非小细胞肺癌(aNSCLC)患者中,PD-L1表达≥90%与更长的生存期相关。我们试图利用来自美国各地社区肿瘤医疗实践的真实世界数据来重现这一发现。
对使用全国性、去识别化的纵向电子健康记录衍生的真实世界数据库,一线开始帕博利珠单抗单药治疗且PD-L1表达≥50%的aNSCLC患者进行回顾性队列研究。感兴趣的暴露因素是PD-L1表达极高,定义为≥90%,与之相比,PD-L1表达高定义为50%至89%。主要结局是总生存期,从开始使用帕博利珠单抗至死亡日期进行测量,末次医疗接触时进行截尾。采用多重填补法填补缺失的协变量。基于倾向评分的逆概率加权法(IPW)用于处理Kaplan-Meier曲线和Cox比例风险回归模型中的混杂因素。
该队列包括1952例接受一线帕博利珠单抗单药治疗的aNSCLC患者。队列成员一半为女性,中位年龄为73岁(四分位间距,65 - 80岁),71%为非鳞状组织学类型,94%有吸烟史,46%的患者PD-L1表达极高。在倾向评分加权样本中,PD-L1表达极高患者的中位总生存期为15.84个月,PD-L1表达高的患者为12.72个月。PD-L1表达极高与较低的死亡风险相关(IPW风险比0.79,95%置信区间0.69 - 0.91)。
在这个美国大型队列中,接受一线帕博利珠单抗治疗的PD-L1表达极高(≥90%)的aNSCLC患者的中位生存期优于PD-L1表达高(50%至89%)的患者。