Intrathecal pemetrexed in NSCLC patients with leptomeningeal metastasis

Spread of lung cancer to the leptomeninges is rare and difficult to treat. Standard therapy comprises CNS-penetrant targeted agents with or without intrathecal chemotherapy. We performed a retrospective analysis of 16 patients with advanced NSCLC and leptomeningeal disease treated with intrathecal pemetrexed 50 mg. All tumours were adenocarcinoma histology; 13 (81.3%) had EGFR mutations, and 3 (18.8%) had no targetable mutations. Prior therapies included EGFR-directed tyrosine kinase inhibitors (TKI) with/ without chemotherapy/antiangiogenic agents (9 [56.3%]), chemotherapy alone (4 [25%]), intrathecal methotrexate with/without hydrocortisone (3 [18.9%]), and radiation (12 [75%]). Presenting symptoms of leptomeningeal disease included headaches (10 [62.5%]), dizziness (8 [50%]), and seizures (7 [43.8%]). Systemic therapy administered along with intrathecal pemetrexed included osimertinib (5 [31.3%]), gefitinib in 1 (6.3%), chemotherapy in 4 (25%) (pemetrexed + carboplatin-2, cisplatin + etoposide-1, paclitaxel-1), chemotherapy + oral TKI in 5 (31.3%) and no systemic therapy in 1 (6.3%). Neurological symptoms following intrathecal pemetrexed included headaches in 1 (6.3%) patient which was likely due to raised intracranial pressure from underlying leptomeningeal disease, and anxiety/uneasiness in 1 (6.3%). Grade 3 or higher [25%]), febrile neutropenia (3 [18.8%]), mucositis (4 [25%]), diarrhoea (1 [6.3%]), rash (1 [6.3%]) and hypokalemia (1 [6.3%]. Most toxicities were likely caused by systemic chemodition (1 [6.3%]). Median OS from diagnosis of leptomeningeal disease was 7.5 months