Wu Shugui, Qiu Zhengang, Shi Huaqiu, Yu Wei, Liu Linfang, Wu Longqiu, Zhong Wenjuan
Department of Oncology, The Affiliated Ganzhou Hospital, Jiangxi Medical College, Nanchang University, Ganzhou, Jiangxi, China.
Department of Oncology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, China.
BMC Cancer. 2025 May 23;25(1):926. doi: 10.1186/s12885-025-14337-z.
Leptomeningeal metastasis in EGFR-mutant (EGFRm) non-small-cell lung cancer (NSCLC) is a severe complication particularly prevalent in patients who have previously been treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, an optimal treatment strategy for dealing with leptomeningeal metastases in patients with NSCLC has yet to be developed. High-dose EGFR-TKIs in combination with intrathecal chemotherapy may offer a promising treatment strategy for this patient population.
We retrospectively identified patients with EGFRm NSCLC who were diagnosed at the First Affiliated Hospital of Gannan Medical University between January 1, 2018, and December 31, 2023. All patients developed leptomeningeal metastases after EGFR-TKI treatment and then received intrathecal pemetrexed chemotherapy in combination with high-dose third-generation EGFR-TKIs (osimertinib 160 mg/day, furmonertinib 160 mg/day, or aumolertinib 165 mg/day), with or without other therapies. Intracranial response, intracranial progression-free survival, overall survival, and safety were evaluated.
Twenty-three patients were enrolled. The median follow-up was 20 months (range, 2-35). The median number of intrathecal pemetrexed injections was 4 (range, 2-26). The intracranial symptom relief rate was 91.3% (21/23), intracranial disease control rate was 86.96% (20/23), median intracranial progression-free survival was 10 months (95% CI, 1.52-18.48), and median overall survival was 12 months (95% CI, 5.43-18.57). The most frequent adverse event was myelosuppression (n = 10, 43.48%), which was limited to grade 1 or 2. Two grade 3 adverse events were observed, including one case of interstitial pneumonia and one case of diarrhea. Univariate and multivariate analyses demonstrated that the combination of bevacizumab and an Eastern Cooperative Oncology Group performance status of ≤ 1 were favorable prognostic factors for survival.
High-dose third-generation EGFR-TKIs combined with pemetrexed intrathecal chemotherapy demonstrated a high rate of intracranial symptom relief and manageable safety in patients with EGFRm NSCLC who developed leptomeningeal metastases after previous EGFR-TKI therapy.
表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）发生软脑膜转移是一种严重并发症，在既往接受过EGFR酪氨酸激酶抑制剂（EGFR-TKIs）治疗的患者中尤为常见。然而，NSCLC患者软脑膜转移的最佳治疗策略尚未确立。高剂量EGFR-TKIs联合鞘内化疗可能为这类患者提供一种有前景的治疗策略。
我们回顾性纳入了2018年1月1日至2023年12月31日期间在赣南医学院第一附属医院确诊的EGFR突变NSCLC患者。所有患者在EGFR-TKI治疗后发生软脑膜转移，随后接受鞘内培美曲塞化疗联合高剂量第三代EGFR-TKIs（奥希替尼160mg/天、伏美替尼160mg/天或阿美替尼165mg/天），可联合或不联合其他治疗。评估颅内反应、颅内无进展生存期、总生存期和安全性。
共纳入23例患者。中位随访时间为20个月（范围2-35个月）。鞘内培美曲塞注射的中位次数为4次（范围2-26次）。颅内症状缓解率为91.3%（21/23），颅内疾病控制率为86.96%（20/23），中位颅内无进展生存期为10个月（95%CI，1.52-18.48），中位总生存期为12个月（95%CI，5.43-18.57）。最常见的不良事件是骨髓抑制（n=10，43.48%），均为1或2级。观察到2例3级不良事件，包括1例间质性肺炎和1例腹泻。单因素和多因素分析表明，贝伐单抗联合东部肿瘤协作组（ECOG）体能状态≤1是生存的有利预后因素。
高剂量第三代EGFR-TKIs联合培美曲塞鞘内化疗在既往接受EGFR-TKI治疗后发生软脑膜转移的EGFR突变NSCLC患者中显示出较高的颅内症状缓解率和可控的安全性。
