DOI: https://doi.org/10.36347/sjmcr.2026.v14i02.002

Pages: 187-190

Leptomeningeal metastases represent one of the most severe complications of epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC) and are associated with substantial neurological morbidity and poor prognosis. Although osimertinib, a third-generation EGFR tyrosine kinase inhibitor, demonstrates superior central nervous system penetration compared with earlier-generation agents, isolated leptomeningeal progression may still occur due to pharmacokinetic sanctuary within the cerebrospinal fluid. We report the case of a 66-year-old man with metastatic EGFR-mutant lung adenocarcinoma who achieved durable systemic disease control with standard-dose osimertinib for 23 months before developing isolated leptomeningeal metastases confirmed by cerebrospinal fluid cytology. Given the stability of extracranial disease, therapeutic intensification with high-dose osimertinib at 160 mg daily combined with intrathecal pemetrexed was initiated, resulting in rapid neurological improvement and meaningful clinical stabilization. Neurological control was maintained for several months, and the patient survived nine months following treatment escalation. This report highlights the potential role of individualized central nervous system–directed strategies in selected patients with EGFR-mutant NSCLC and leptomeningeal progression.