# Efficacy and Safety Evaluation of Intrathecal Pemetrexed in EGFR-mutated NSCLC Patients with Leptomeningeal Metastases

## TL;DR

This study evaluates the effectiveness and safety of intrathecal pemetrexed in treating brain cancer patients with specific genetic mutations and leptomeningeal metastases.

## Contribution

The study provides real-world data on the efficacy and safety of intrathecal pemetrexed in EGFR-mutated NSCLC patients with leptomeningeal metastases.

## Key findings

- Intrathecal pemetrexed showed a 77.9% clinical response rate in treated patients.
- Patients with higher KPS scores had significantly longer survival times.
- Combining pemetrexed with bevacizumab improved survival outcomes.

## Abstract

软脑膜转移（leptomeningeal metastasis, LM）在晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者中的发病率逐年上升，但其治疗手段有限，预后较差。鞘内注射培美曲塞（intrathecal Pemetrexed, IP）在LM治疗领域具有广泛的应用前景。本研究旨在评估IP在表皮生长因子受体（epidermal growth factor receptor, EGFR）突变阳性NSCLC-LM患者中的疗效、安全性及最佳联合应用模式，以期为此类患者探寻更精准的个体化治疗策略提供真实世界数据支持。

回顾性收集2018年1月至2024年6月在南京大学医学院附属鼓楼医院接受IP治疗的104例EGFR突变阳性NSCLC-LM患者的临床资料、治疗方案和生存数据。系统分析入组患者的总生存期（overall survival, OS）、无进展生存期（progression-free survival, PFS）、临床有效率和不良反应（adverse events, AEs）。

104例EGFR突变阳性NSCLC-LM患者的中位PFS为9.6个月，中位OS为13.0个月，6个月和1年OS率分别为80.8%和56.5%，临床有效率为77.9%。常见的AEs是骨髓抑制（58.7%）和转氨酶升高（25.0%）。9例（8.7%）患者出现4级骨髓抑制，给予对症治疗后恢复正常。亚组分析显示，卡氏体能状态（Karnofsky performance status, KPS）评分≥60分的患者OS显著长于KPS<60分患者（14.4 vs 9.0个月，P=0.0022）。规律接受贝伐珠单抗治疗的LM患者中位OS明显高于未接受贝伐珠单抗治疗者（19.2 vs 10.5个月，P=0.0011）。

IP治疗在EGFR突变阳性NSCLC-LM患者中具有良好的疗效和安全性，联合贝伐珠单抗可发挥协同抗肿瘤作用，进一步改善预后。

Clinical characteristics of patients with NSCLC-LM (n=104)

Clinical symptoms of NSCLC-LM patients (n=104)

Clinical response assessment after IP therapy

A: Survival curve of KPS≥60 and KPS<60 group; B: The unadjusted and adjusted HR for mortality in KPS≥60 group and the KPS<60 group; C: Survival curve of Bevacizumab group and without Bevacizumab group; D: The unadjusted and adjusted HR for mortality in Bevacizumab group and without Bevacizumab group. BEV: Bevacizumab; C: chemotherapy; R: radiotherapy; HR: hazard ratio.

A: Survival curve of common EGFR mutation and uncommon EGFR mutation group; B: Survival curve of brain metastasis and without brain metastasis group; C: Survival curve of ECM group and without ECM group; D: Survival curve of Ommaya reservoir and without Ommaya reservoir group; E: Survival curve of systemic chemotherapy and without chemotherapy group; F: Survival curve of brain radiotherapy and without brain radiotherapy group. ECM: extra-CNS metastasis.

Adverse events evaluation after IP therapy (n=104)