Liu Jia, Itchins Malinda, Nagrial Adnan, Cooper Wendy A, De Silva Madhawa, Barnet Megan, Varikatt Winny, Sivasubramaniam Vanathi, Davis Alexander, Gill Anthony J, Blinman Prunella, Lee Kenneth, Hui Rina, Gao Bo, Pavlakis Nick, Clarke Stephen, Lee Jenny, Boyer Michael, Kao Steven
Crown Princess Mary Cancer Centre, Westmead, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Children's Medical Research Institute, Westmead, NSW, Australia.
Northern Clinical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia.
Lung Cancer. 2021 May;155:28-33. doi: 10.1016/j.lungcan.2021.03.004. Epub 2021 Mar 9.
Predictive biomarkers for poor response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is an area of ongoing research. This multicentre retrospective study sought to determine the impact of programmed death-ligand 1 (PD-L1) tumour proportional score (TPS) on outcome in EGFR TKI treated patients.
Patients with Stage IIIB/IV lung adenocarcinoma harbouring a sensitising EGFR mutation treated with first-line TKI at five metropolitan hospitals were included. PD-L1 TPS was determined using the Ventana anti-PD-L1 (SP263) assay. High PD-L1 expression was defined as TPS ≥ 50 %. Determinants of progression and survival hazards were modelled using Cox regression.
A total of 186 patients were included. Mean age was 67 years, 66 % were female and 54 % were Asian. Patients with high PD-L1 expression (n = 23; 12 %) had significantly shorter progression free survival (6.6 vs 13.0 months, hazard ratio (HR) 2.6 95 % CI 1.6-4.2, p < 0.0001) and overall survival (11.5 vs 32.9 months, HR 3.3, 95 % CI 1.9-5.7, p < 0.0001) compared to patients with PD-L1 low/negative tumours. This remained significant in multivariate analyses. High PD-L1 in post-TKI progression biopsies was not associated with poorer survival.
In this large, real-world cohort of EGFR-mutant lung adenocarcinoma patients, high PD-L1 expression was associated with early resistance to 1st generation EGFR TKIs and shorter survival, regardless of ethnicity.
预测表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）疗效不佳的生物标志物是一个正在进行研究的领域。这项多中心回顾性研究旨在确定程序性死亡配体1（PD-L1）肿瘤比例评分（TPS）对接受EGFR TKIs治疗患者结局的影响。
纳入在五家大城市医院接受一线TKI治疗、携带敏感EGFR突变的IIIB/IV期肺腺癌患者。使用Ventana抗PD-L1（SP263）检测法测定PD-L1 TPS。高PD-L1表达定义为TPS≥50%。使用Cox回归对进展和生存风险的决定因素进行建模。
共纳入186例患者。平均年龄为67岁，66%为女性，54%为亚洲人。与PD-L1低/阴性肿瘤患者相比，高PD-L1表达患者（n = 23；12%）的无进展生存期显著缩短（6.6个月对13.0个月，风险比（HR）2.6，95%置信区间1.6 - 4.2，p < 0.0001）和总生存期显著缩短（11.5个月对32.9个月，HR 3.3，95%置信区间1.9 - 5.7，p < 0.0001）。在多变量分析中，这一结果仍然显著。TKI治疗后进展活检中高PD-L1与较差的生存率无关。
在这个大型的、真实世界的EGFR突变肺腺癌患者队列中，无论种族如何，高PD-L1表达都与对第一代EGFR TKIs的早期耐药和较短生存期相关。
