Survival Outcomes in EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases: Kaplan–Meier and Cox Regression Analyses Across Treatment Stages

IF 2.3 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal Pub Date : 2025-05-27 DOI:10.1111/crj.70085

Haoran Qi, Qiang Qiao, Xiaorong Sun, Ligang Xing

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引用次数: 0

Abstract

Background

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown significant efficacy in patients with brain metastases (BMs) from EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance is inevitable, and clinical data addressing key questions across treatment stages remain insufficient, limiting the formulation of precise treatment strategies.

Methods

This retrospective study analyzed 302 EGFR-mutant NSCLC patients with BMs treated at Shandong Cancer Hospital (2014–2022). Patients were divided into three cohorts: cohort A (first-/second-generation EGFR-TKIs without third-generation use), cohort B (first-/second-generation followed by third-generation EGFR-TKIs), and cohort C (first-line third-generation EGFR-TKIs). Survival outcomes were evaluated using Kaplan–Meier and Cox regression analyses across three treatment stages. Propensity score matching (PSM) adjusted for baseline imbalances.

Results

Third-generation EGFR-TKIs demonstrated superior progression-free survival (PFS) in first-line therapy compared to earlier-generation agents (median PFS1: 14.2 vs. 11.2 months; p = 0.0021), particularly for intracranial control (median iPFS1: 18.0 vs. 12.2 months; p = 0.0058). Patients with uncommon EGFR mutations had significantly shorter PFS on third-generation EGFR-TKIs than those with common mutations (4.4 vs. 12.9 months; p = 0.012). After resistance, combination therapy with immune checkpoint inhibitors (ICIs), antiangiogenics, and chemotherapy extended overall survival (OS) versus non-ICI regimens (median OS2: 17.3 vs. 10.4 months; p = 0.004).

Conclusions

Third-generation EGFR-TKIs are effective first-line options for BMs but show limited efficacy against uncommon mutations. Post-resistance regimens integrating ICIs, antiangiogenics, and chemotherapy may improve survival. Reassessment of genetic and PD-L1 status is critical for guiding sequential therapy.

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egfr突变的非小细胞肺癌脑转移患者的生存结局：Kaplan-Meier和Cox回归分析

表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）在egfr突变的非小细胞肺癌（NSCLC）脑转移（BMs）患者中显示出显著疗效。然而，获得性耐药是不可避免的，跨治疗阶段解决关键问题的临床数据仍然不足，限制了精确治疗策略的制定。方法回顾性分析2014-2022年山东省肿瘤医院收治的302例egfr突变非小细胞肺癌脑转移患者。患者被分为三个队列：队列A（第一代/第二代未使用第三代EGFR-TKIs），队列B（第一代/第二代随后使用第三代EGFR-TKIs）和队列C（一线第三代EGFR-TKIs）。使用Kaplan-Meier和Cox回归分析评估三个治疗阶段的生存结果。倾向得分匹配（PSM）调整基线不平衡。与前代药物相比，第三代EGFR-TKIs在一线治疗中表现出更高的无进展生存期（PFS）(中位PFS1: 14.2个月vs 11.2个月；p = 0.0021)，特别是颅内控制(中位iPFS1: 18.0 vs. 12.2个月；p = 0.0058)。具有罕见EGFR突变的患者在第三代EGFR- tkis上的PFS明显短于具有常见突变的患者(4.4个月vs 12.9个月；p = 0.012)。耐药后，与非ici方案相比，免疫检查点抑制剂（ICIs）、抗血管生成药物和化疗联合治疗延长了总生存期（OS）(中位OS2: 17.3 vs 10.4个月；p = 0.004)。结论：第三代EGFR-TKIs是治疗脑转移的有效一线选择，但对罕见突变的疗效有限。耐药后的治疗方案整合了ICIs、抗血管生成药物和化疗，可以提高生存率。重新评估遗传和PD-L1状态对于指导序贯治疗至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Respiratory Journal 医学-呼吸系统

CiteScore

3.70

自引率

0.00%

发文量

104

审稿时长

>12 weeks

期刊介绍： Overview Effective with the 2016 volume, this journal will be published in an online-only format. Aims and Scope The Clinical Respiratory Journal (CRJ) provides a forum for clinical research in all areas of respiratory medicine from clinical lung disease to basic research relevant to the clinic. We publish original research, review articles, case studies, editorials and book reviews in all areas of clinical lung disease including: Asthma Allergy COPD Non-invasive ventilation Sleep related breathing disorders Interstitial lung diseases Lung cancer Clinical genetics Rhinitis Airway and lung infection Epidemiology Pediatrics CRJ provides a fast-track service for selected Phase II and Phase III trial studies. Keywords Clinical Respiratory Journal, respiratory, pulmonary, medicine, clinical, lung disease, Abstracting and Indexing Information Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Embase (Elsevier) Health & Medical Collection (ProQuest) Health Research Premium Collection (ProQuest) HEED: Health Economic Evaluations Database (Wiley-Blackwell) Hospital Premium Collection (ProQuest) Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) ProQuest Central (ProQuest) Science Citation Index Expanded (Clarivate Analytics) SCOPUS (Elsevier)