You Mengxing, Wu Lige, Liu Jiayu, Yuan Hanqi, Wang Zihe, Hao Xuezhi, Xing Puyuan, Li Junling
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Thorac Cancer. 2025 Jun;16(11):e70095. doi: 10.1111/1759-7714.70095.
Optimal treatment for driver gene-negative non-small cell lung cancer (NSCLC) with brain metastases (BM) remains unclear, particularly regarding immune checkpoint inhibitor (ICI)-based combinations and local BM therapy. Predictive biomarkers for intracranial efficacy are also undefined.
This retrospective study analyzed driver gene-negative NSCLC patients with BM treated with first-line ICI-based systemic therapy (ICI plus chemotherapy [ICI + CT] or ICI + CT plus bevacizumab [ICI + CT + Bev]) from June 2019 to June 2024. The intracranial progression-free survival (icPFS), progression-free survival (PFS), and overall survival (OS) were compared between treatment groups and by BM local therapy. The PD-L1 tumor proportion score (TPS) expression was evaluated for correlation with intracranial efficacy.
A total of 36 patients were enrolled in the study. The intracranial objective response rate (icORR) was 70.6% (ICI + CT) versus 78.6% (ICI + CT + Bev) (p = 0.689), with no significant differences in icPFS, PFS, or OS between the two different first-line systemic regimens (all p > 0.05). Local BM therapy (n = 18) did not improve icPFS and OS (all p > 0.05). Extracranial PD-L1 (TPS ≥ 50%, n = 13) correlated with superior icPFS, PFS, and OS (all p < 0.05) versus PD-L1 TPS < 50%. Multivariate analysis confirmed PD-L1 ≥ 50% as an independent prognostic factor (HR = 0.155; 95% CI, 0.025-0.939; p = 0.042).
Adding bevacizumab to first-line ICI-chemotherapy did not enhance survival outcomes. Local treatment for BM did not provide additional survival advantages when combined with first-line ICI-based systemic therapy. Extracranial PD-L1 TPS ≥ 50% predicted improved intracranial efficacy.
驱动基因阴性的非小细胞肺癌（NSCLC）伴脑转移（BM）的最佳治疗方案仍不明确，尤其是基于免疫检查点抑制剂（ICI）的联合治疗以及局部脑转移治疗。颅内疗效的预测生物标志物也尚未明确。
这项回顾性研究分析了2019年6月至2024年6月期间接受一线基于ICI的全身治疗（ICI加化疗[ICI + CT]或ICI + CT加贝伐单抗[ICI + CT + Bev]）的驱动基因阴性的NSCLC伴脑转移患者。比较了治疗组之间以及根据脑转移局部治疗情况的颅内无进展生存期（icPFS）、无进展生存期（PFS）和总生存期（OS）。评估了PD-L1肿瘤比例评分（TPS）表达与颅内疗效的相关性。
共有36例患者纳入研究。颅内客观缓解率（icORR）在ICI + CT组为70.6%，在ICI + CT + Bev组为78.6%（p = 0.689），两种不同的一线全身治疗方案在icPFS、PFS或OS方面无显著差异（所有p > 0.05）。局部脑转移治疗（n = 18）未改善icPFS和OS（所有p > 0.05）。与PD-L1 TPS < 50%相比，颅外PD-L1（TPS≥50%，n = 13）与更好的icPFS、PFS和OS相关（所有p < 0.05）。多因素分析证实PD-L1≥50%是独立的预后因素（HR = 0.155；95%CI，0.025 - 0.939；p = 0.042）。
在一线ICI化疗中添加贝伐单抗并未提高生存结局。脑转移的局部治疗与一线基于ICI的全身治疗联合使用时，并未提供额外的生存优势。颅外PD-L1 TPS≥50%预示颅内疗效改善。
