Zhang Yidan, Xu Yingqi, Jin Hongping, Liu Tengfei, Zhong Hua, Xu Jianlin, Lou Yuqing, Zhong Runbo
Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cancer Sci. 2025 Jun;116(6):1648-1660. doi: 10.1111/cas.70060. Epub 2025 Mar 18.
The association between the spatial heterogeneity of programmed cell death ligand 1 (PD-L1) expression and the efficacy of third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) remains elusive. This retrospective study analyzed data from 4171 NSCLC patients with EGFR-sensitive mutations treated at Shanghai Chest Hospital from August 2019 to September 2023. Among them, 182 patients receiving third-generation EGFR-TKIs monotherapy as a first-line treatment were enrolled. Patients were categorized by biopsy sites into primary lung lesions (n = 112) and metastatic lymph nodes (n = 70). PD-L1 expression was stratified based on tumor cell proportion score (TPS): < 1%, 1%-49%, and ≥ 50%. The median progression-free survival (PFS) for the entire cohort was 18.33 months. In the PD-L1 TPS group, PFS was 18.87 months for TPS < 1%, 17.6 months for TPS 1%-49%, and 13.6 months for TPS ≥ 50%, with significant differences across groups (p = 0.026). Moreover, multivariate analysis identified smoking history [HR = 1.653, 95% CI (1.132-2.414), p = 0.009] and TPS ≥ 50% [HR = 2.069, 95% CI (1.183-3.618), p = 0.011] as independent risk factors. In primary lesions, the median PFS was 21.93 months for TPS < 1%, 18.57 months for TPS 1%-49%, and 10.17 months for TPS ≥ 50%, with significant differences (p < 0.001). However, PD-L1 expression in metastatic lymph nodes was not associated with PFS (p = 0.973). In advanced EGFR-mutant NSCLC, high PD-L1 expression may suggest reduced efficacy of third-generation EGFR-TKIs. The spatial heterogeneity of PD-L1 expression could influence its predictive accuracy for third-generation EGFR-TKI efficacy.
程序性细胞死亡配体1（PD-L1）表达的空间异质性与第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）在表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）中的疗效之间的关联仍不明确。这项回顾性研究分析了2019年8月至2023年9月在上海胸科医院接受治疗的4171例EGFR敏感突变的NSCLC患者的数据。其中，182例接受第三代EGFR-TKIs单药一线治疗的患者被纳入研究。患者按活检部位分为原发性肺病变（n = 112）和转移性淋巴结（n = 70）。根据肿瘤细胞比例评分（TPS）对PD-L1表达进行分层：<1%、1%-49%和≥50%。整个队列的中位无进展生存期（PFS）为18.33个月。在PD-L1 TPS组中，TPS<1%时PFS为18.87个月，TPS 1%-49%时为17.6个月，TPS≥50%时为13.6个月，各组间存在显著差异（p = 0.026）。此外，多因素分析确定吸烟史[风险比（HR）= 1.653，95%置信区间（CI）（1.132 - 2.414），p = 0.009]和TPS≥50%[HR = 2.069，95%CI（1.183 - 3.618），p = 0.011]为独立危险因素。在原发性病变中，TPS<1%时中位PFS为21.93个月，TPS 1%-49%时为18.57个月，TPS≥50%时为10.17个月，差异有统计学意义（p < 0.001）。然而，转移性淋巴结中的PD-L1表达与PFS无关（p = 0.973）。在晚期EGFR突变的NSCLC中，高PD-L1表达可能提示第三代EGFR-TKIs疗效降低。PD-L1表达的空间异质性可能影响其对第三代EGFR-TKI疗效的预测准确性。
