Thoracic Oncology Unit, Pneumology, Cochin Hospital AP-HP Paris, Paris, France.
Thoracic Oncology, Georges-Pompidou European Hospital, AP-HP Paris, Paris, France.
PLoS One. 2024 Nov 7;19(11):e0307161. doi: 10.1371/journal.pone.0307161. eCollection 2024.
Recent evidence suggests that elevated levels of PD-L1 expression may be linked to early resistance to TKI and reduced survival in NSCLC with EGFR mutations. This study aimed to characterize the clinical and molecular features of EGFR-mutated lung adenocarcinomas and determine the prognostic significance associated with high PD-L1 expression.
We conducted a retrospective chart review of 103 consecutive patients with advanced EGFR-mutated NSCLC, who received treatment between 01/01/2016 and 30/12/2020, at our institution.
Among the tumors, 17% (n = 18) exhibited high PD-L1 expression (≥50% tumor proportion score), which was associated with a lower prevalence of common EGFR mutations (56% vs. 82%, p = 0.03) and a higher frequency of complex EGFR mutations (28% vs. 7%, p = 0.02). Univariate analysis did not reveal any significant differences in first-line response, progression-free survival, or overall survival between the PD-L1 ≥50% and <50% groups. However, multivariate analysis demonstrated that PD-L1 ≥50% was independently associated with shorter survival (HR = 2.57; 95%CI[1.20-5.55]; p = 0.02), along with male gender (HR = 2.77; 95%CI[1.54-4.19]; p<0.005), presence of liver metastases (HR = 5.80; 95%CI[2.86-11.75]; p<0.005) or brain metastases (HR = 1.99; 95%CI[1.13-3.52]; p = 0.02), and poor general condition at diagnosis (ECOG 3 and 4) (HR = 10.69; 95% CI[4.42-25.85]; p<0.005). Additionally, a trend towards a higher frequency of de novo resistance was observed in the PD-L1 >50% group (7% vs. 17%, p = 0.19).
High PD-L1 expression was more commonly found in lung adenocarcinomas with uncommon and complex EGFR mutations. Furthermore, high PD-L1 expression independently predicted poor survival. These findings warrant validation through prospective studies.
最近的证据表明，PD-L1 表达水平升高可能与 EGFR 突变的非小细胞肺癌（NSCLC）患者对 TKI 的早期耐药和生存时间缩短有关。本研究旨在分析 EGFR 突变型肺腺癌的临床和分子特征，并确定与高 PD-L1 表达相关的预后意义。
我们对在我院接受治疗的 103 例连续的晚期 EGFR 突变型 NSCLC 患者进行了回顾性病历审查，入组时间为 2016 年 1 月 1 日至 2020 年 12 月 30 日。
在这些肿瘤中，有 17%（n=18）表现出高 PD-L1 表达（肿瘤比例评分≥50%），这与常见 EGFR 突变的发生率较低（56%比 82%，p=0.03）和复杂 EGFR 突变的发生率较高（28%比 7%，p=0.02）相关。单因素分析显示，PD-L1≥50%组与<50%组之间在一线治疗反应、无进展生存期和总生存期方面均无显著差异。然而，多因素分析表明，PD-L1≥50%与较短的生存期独立相关（HR=2.57；95%CI[1.20-5.55]；p=0.02），同时与男性（HR=2.77；95%CI[1.54-4.19]；p<0.005）、肝转移（HR=5.80；95%CI[2.86-11.75]；p<0.005）或脑转移（HR=1.99；95%CI[1.13-3.52]；p=0.02）的存在以及诊断时一般状况较差（ECOG 3 和 4）（HR=10.69；95%CI[4.42-25.85]；p<0.005）有关。此外，在 PD-L1>50%组中观察到新发耐药的频率更高（7%比 17%，p=0.19）。
高 PD-L1 表达在罕见和复杂 EGFR 突变的肺腺癌中更为常见。此外，高 PD-L1 表达独立预测不良预后。这些发现需要通过前瞻性研究进行验证。
