Posado-Domínguez Luis, Olivares-Hernández Alejandro, Morchón-Araujo Daniel, Figuero-Perez Luis, Bellido-Hernández Lorena, Corvo-Felix Laura, Roldan-Ruiz Jonnathan, San Miguel Iñigo, Fonseca-Sanchez Emilio, Del Barco-Morillo Edel
Medical Oncology Department, University Hospital of Salamanca, Salamanca, Spain.
Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
Transl Lung Cancer Res. 2025 Jul 31;14(7):2494-2508. doi: 10.21037/tlcr-2025-65. Epub 2025 Jul 18.
The prognostic significance of TTF-1 expression in advanced lung adenocarcinoma may be an important factor in optimizing treatment strategies. This study aimed to evaluate the impact of TTF-1 negativity on overall survival (OS) and progression-free survival (PFS) in stage IV lung adenocarcinoma patients with low PD-L1 expression treated with platinum-pemetrexed-pembrolizumab.
We conducted a retrospective analysis of 155 patients with stage IV lung adenocarcinoma and PD-L1 expression <50%. We stratified patients according to TTF-1 expression. The primary survival analysis focused on 64 patients who received first-line platinum-pemetrexed chemotherapy in combination with pembrolizumab. We evaluated OS and PFS using Kaplan-Meier curves and multivariate Cox regression.
Among patients treated with platinum-pemetrexed-pembrolizumab, TTF-1-negative patients showed significantly shorter OS and numerically shorter PFS compared to TTF-1-positive patients. Median OS was 13 months for TTF-1-negative patients and 21 months for TTF-1-positive patients (P=0.01). Median PFS was 10 13 months, respectively (P=0.11). In the overall cohort, TTF-1 negativity was independently associated with a 2.3-fold increased risk of mortality (hazard ratio =2.288, 95% confidence interval: 1.073-4.879, P=0.03).
TTF-1 negativity is an independent adverse prognostic factor in patients with stage IV lung adenocarcinoma and low PD-L1 expression. The observed differences in survival suggest that platinum-pemetrexed-pembrolizumab may be less effective for TTF-1-negative patients, and that alternative strategies should be explored in this high-risk subgroup.
在晚期肺腺癌中，甲状腺转录因子-1（TTF-1）表达的预后意义可能是优化治疗策略的重要因素。本研究旨在评估TTF-1阴性对接受铂类-培美曲塞-帕博利珠单抗治疗的IV期肺腺癌且程序性死亡配体-1（PD-L1）低表达患者总生存期（OS）和无进展生存期（PFS）的影响。
我们对155例IV期肺腺癌且PD-L1表达<50%的患者进行了回顾性分析。根据TTF-1表达对患者进行分层。主要生存分析集中于64例接受一线铂类-培美曲塞化疗联合帕博利珠单抗治疗的患者。我们使用Kaplan-Meier曲线和多因素Cox回归评估OS和PFS。
在接受铂类-培美曲塞-帕博利珠单抗治疗的患者中，与TTF-1阳性患者相比，TTF-1阴性患者的OS显著缩短，PFS在数值上也较短。TTF-1阴性患者的中位OS为13个月，TTF-1阳性患者为21个月（P=0.01）。中位PFS分别为10个月和13个月（P=0.11）。在整个队列中，TTF-1阴性与死亡风险增加2.3倍独立相关（风险比=2.288，95%置信区间：1.073-4.879，P=0.03）。
TTF-1阴性是IV期肺腺癌且PD-L1低表达患者的独立不良预后因素。观察到的生存差异表明，铂类-培美曲塞-帕博利珠单抗对TTF-1阴性患者可能效果较差，应在这一高危亚组中探索替代策略。
