Li Liqun, Huang Zhe, Chen Yangqian, Ma Hongzhi, Chen Xiaoquan, Yan Huan, Qin Haoyue, Zhang Yuda, Zhang Xing, Jiang Wenjuan, Wang Zhan, Zhang Lin, Zeng Fanxu, Zhou Zhiguo, Pu Xingxiang, Yang Nong, Zeng Liang, Zhang Yongchang
Department of Medical Anesthesia, Pain Ward, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.
Heliyon. 2024 Dec 7;10(24):e40703. doi: 10.1016/j.heliyon.2024.e40703. eCollection 2024 Dec 30.
This study assessed the impact of intrathecal pemetrexed (IP) in managing leptomeningeal metastases (LM) in previously treated patients with -mutant advanced non-small cell lung cancer (NSCLC).
We analyzed the clinical and survival outcomes of 50 patients with LM who received 50 mg IP after disease progression with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment between September 2021 and September 2023 at the Hunan Cancer Hospital. Treatment response was evaluated based on improvement in neurological symptoms/signs and Karnofsky Performance Status (KPS) scores. We also evaluated the overall survival (OS), intracranial progression-free survival (I-PFS), and extracranial progression-free survival (E-PFS). Next generation sequencing (NGS) was employed to explore the underlying mechanisms of LM after EGFR-TKIs resistance.
IP treatment was associated with a 64 % clinical response rate, median I-PFS of 5.3 months (95 % confidence intervals [CI], 1.4-9.2), E-PFS of 8.0 months (95 % CI, 2.2-13.8), and OS of 12.0 months (95 % CI, 9.6-14.4). Compared with non-responders, responders to IP demonstrated significantly prolonged I-PFS (11.2 months vs. 1.0 month; hazard ratio [HR]: 0.15, 95 % CI: 0.06-0.39), E-PFS (11.2 months vs. 3.0 months; HR: 0.24, 95 % CI: 0.10-0.57), and OS (15.5 months vs. 3.8 months; HR: 0.22, 95 % CI: 0.08-0.58) (all P < 0.001). Adverse events(AEs) primarily consisted of myelosuppression (54 %) and hepatic damage (24 %), but were manageable and did not result in any deaths. mutations were consistent between cerebrospinal fluid (CSF) and primary tumors in 100 % of cases. CSF also exhibited genetic variations such as mutations/amplifications and alterations in , , , and .
IP represents a potentially viable treatment option for managing LM in patients with EGFR-TKI-resistant -mutant advanced NSCLC. Clinical responses as measured by the improvement of neurological symptoms/signs and KPS scores were associated with favorable survival outcomes.
本研究评估了鞘内注射培美曲塞（IP）对既往接受治疗的携带EGFR突变的晚期非小细胞肺癌（NSCLC）患者软脑膜转移（LM）的治疗效果。
我们分析了2021年9月至2023年9月在湖南省肿瘤医院接受治疗的50例LM患者的临床和生存结局，这些患者在表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗疾病进展后接受了50mg的IP治疗。根据神经症状/体征的改善情况和卡诺夫斯基功能状态（KPS）评分评估治疗反应。我们还评估了总生存期（OS）、颅内无进展生存期（I-PFS）和颅外无进展生存期（E-PFS）。采用二代测序（NGS）探索EGFR-TKIs耐药后LM的潜在机制。
IP治疗的临床缓解率为64%，中位I-PFS为5.3个月（95%置信区间[CI]，1.4-9.2），E-PFS为8.0个月（95%CI，2.2-13.8），OS为12.0个月（95%CI，9.6-14.4）。与无反应者相比，IP反应者的I-PFS（11.2个月对1.0个月；风险比[HR]：0.15，95%CI：0.06-0.39）、E-PFS（11.2个月对3.0个月；HR：0.24，95%CI：0.10-0.57）和OS（15.5个月对3.8个月；HR：0.22，95%CI：0.08-0.58）均显著延长（所有P<0.001）。不良事件（AE）主要包括骨髓抑制（54%）和肝损伤（24%），但可控制，未导致任何死亡。100%的病例中脑脊液（CSF）和原发性肿瘤之间的EGFR突变一致。CSF还表现出基因变异，如KRAS突变/扩增以及NRAS、BRAF、PIK3CA和AKT1的改变。
IP是治疗EGFR-TKI耐药的携带EGFR突变的晚期NSCLC患者LM的一种潜在可行的治疗选择。通过神经症状/体征和KPS评分改善所衡量的临床反应与良好的生存结局相关。
