Intrathecal pemetrexed in patients with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistant refractory leptomeningeal metastasis lung adenocarcinoma: a retrospective study.

BACKGROUND: The incidence of meningeal metastasis in lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations is rising annually. Refractory meningeal metastasis following EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance presents a significant clinical challenge, lacking effective treatments and often leading to fatal outcomes. This study aims to evaluate the antitumor efficacy and safety of intrathecal pemetrexed in patients with EGFR-TKI-resistant meningeal metastasis.

METHODS: From November 1, 2020 to November 1, 2022, a total of 10 patients were enrolled. All underwent next-generation sequencing (NGS) and carcino-embryonic antigen (CEA) testing of cerebrospinal fluid (CSF). These patients had previously experienced symptomatic and supportive treatment, EGFR-TKI resistance, systemic intravenous chemotherapy, and bevacizumab therapy. Intrathecal pemetrexed was administered at doses of 20 or 40 mg once weekly and was well-tolerated.

RESULTS: The disease control rate (DCR) was 88.8% (8/9), with 10% (1/10) showing negative CSF cytology. Quality of life (QoL) scores improved, and CSF CEA levels decreased. The median progression-free survival (PFS) was 5 months, and the median overall survival (OS) was 8.15 months. Adverse events occurred in 90% of patients, with nausea, vomiting, and myelosuppression being the most common. Grade 3 or higher adverse events were observed in 40% (4/10) of patients, primarily myelosuppression, which improved with systemic treatment. No treatment-related deaths occurred.

CONCLUSIONS: This study suggests that intrathecal pemetrexed can be a viable salvage treatment for refractory meningeal metastasis in EGFR-TKI-resistant lung adenocarcinoma.