Intrathecal pemetrexed in patients with EGFR-TKI resistant refractory leptomeningeal metastasis lung adenocarcinoma : a retrospective study

AbstractThe incidence of meningeal metastasis in lung adenocarcinoma with EGFR mutation is increasing annually. Refractory meningeal metastasis following EGFR-TKI resistance has no effective treatment and a lethal complication of tumors. The purpose of this study was to evaluate the potential antitumor efficacy and safety of intrathecal pemetrexed in patients with EGFR-TKI resistance refractory meningeal metastasis. From November 1, 2020 to November 1 2022, a total of 10 patients were enrolled in the study, and all patients underwent NGS and CEA testing of cerebrospinal fluid. The patients had entered the stage of symptomatic and supportive treatment before intrathecal pemetrexed, experienced EGFR-TKI resistance, systemic intravenous chemotherapy and bevacizumab treatment previously. Intrathecal pemetrexed was well-effective and tolerated, occurring at the 20mg or 40mg once a week dose. The disease control rate of intrathecal injection was 88.8% (8/9); 10% (1/10) had negative cerebrospinal fluid cytology; concurrently, the quality of life (QoL)score improved, and cerebrospinal fluid CEA decreased. The median PFS of intrathecal injection was five months, and the median OS was 8.15 months. Ninety percent of patients experienced adverse events of varying degrees, with nausea, vomiting, and myelosuppression being the most common. The incidence of grade three or higher adverse events was 40% (4/10), primarily myelosuppression, which improved after systemic treatment; no treatment-related deaths occurred.This study suggests intrathecal pemetrexed can be used for salvage treatment of refractory meningeal metastatic in EGFR-TKI resistant lung adenocarcinoma.