Zhuang Lulu, Yin Xiaoyan, Liu Xiaoli, Liu Defeng, Wei Zhonghui, Chen Yu, Zhao Kaikai, Li Yankang, Yu Jinming, Meng Xiangjiao
Shandong University Cancer Center, Jinan, Shandong, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
J Neurooncol. 2025 Apr;172(2):461-470. doi: 10.1007/s11060-025-04938-w. Epub 2025 Feb 4.
To evaluate the efficacy and safety of aumolertinib in treating non-small cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM) and epidermal growth factor receptor (EGFR) mutations.
We conducted a retrospective analysis of clinical data from 79 patients with EGFR-mutated advanced NSCLC treated with aumolertinib after being diagnosed with LM at Shandong Cancer Hospital and Institute between April 2020 and July 2023. We evaluated overall survival (OS), progression-free survival (PFS), LM-PFS, and safety. Patient prognosis was assessed using Kaplan-Meier and Cox regression analyses.
The median follow-up duration was 19.8 months (95% CI: 16.2-23.4), and 16 (20.3%) patients had previously used third-generation EGFR-TKI. The median LM-PFS was 10.6 months (95% CI: 8.6-12.5). The overall response rate (ORR) for LM was 53.2%, while the disease control rate (DCR) reached 91.1%. Among the 67 (84.8%) patients presenting with symptoms attributable to LM, 60 reported improved or stable symptoms. The median OS was 17.7 months (95% CI: 13.7-21.7), while the median PFS was 9.7 months (95% CI: 7.5-11.9). The systemic ORR and DCR were 38.0% and 87.3%, respectively. Multivariate Cox regression analysis identified L858R mutations (hazard ratio [HR] = 2.22, P = 0.030), prior systemic therapy (HR = 3.89, P < 0.001), ECOG PS ≥ 2 (HR = 4.06, P < 0.001) and ≥ 3 extracranial organ metastases (HR = 2.20, P = 0.025) as independent negative predictors of OS. Creatine kinase elevation (HR = 0.41, P = 0.018) was an independent predictor of better OS. Treatment-related adverse events occurred in 61 patients (77.2%), predominantly as grade 1 or 2.
Aumolertinib showed potential in treating EGFR-mutated NSCLC patients with LM, with a tolerable safety profile.
评估奥莫替尼治疗伴有软脑膜转移（LM）且表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者的疗效和安全性。
我们对2020年4月至2023年7月期间在山东省肿瘤医院暨山东省肿瘤防治研究院被诊断为LM后接受奥莫替尼治疗的79例EGFR突变的晚期NSCLC患者的临床资料进行了回顾性分析。我们评估了总生存期（OS）、无进展生存期（PFS）、LM无进展生存期（LM-PFS）和安全性。使用Kaplan-Meier法和Cox回归分析评估患者预后。
中位随访时间为19.8个月（95%CI：16.2-23.4），16例（20.3%）患者曾使用过第三代EGFR-TKI。中位LM-PFS为10.6个月（95%CI：8.6-12.5）。LM的总缓解率（ORR）为53.2%，而疾病控制率（DCR）达到91.1%。在67例（84.8%）出现与LM相关症状的患者中，60例报告症状改善或稳定。中位OS为17.7个月（95%CI：13.7-21.7），而中位PFS为9.7个月（95%CI：7.5-11.9）。全身ORR和DCR分别为38.0%和87.3%。多因素Cox回归分析确定L858R突变（风险比[HR]=2.22，P=0.030）、既往全身治疗（HR=3.89，P<0.001）、东部肿瘤协作组体能状态（ECOG PS）≥ 2（HR=4.06，P<0.001）和≥ 3个颅外器官转移（HR=2.20，P=0.025）是OS的独立负性预测因素。肌酸激酶升高（HR=0.41，P=0.018）是OS较好的独立预测因素。61例（77.2%）患者发生治疗相关不良事件，主要为1级或2级。
奥莫替尼在治疗伴有LM的EGFR突变NSCLC患者中显示出潜力，且安全性可耐受。
