Leptomeningeal Carcinomatosis During Dose-Reduced Osimertinib Therapy in Epidermal Growth Factor Receptor (EGFR) L858R-Mutated Lung Adenocarcinoma: A Case Report.

Leptomeningeal carcinomatosis (LMC) remains a devastating complication of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer despite the availability of central nervous system (CNS)-active EGFR tyrosine kinase inhibitors (TKIs). We report the case of a 77-year-old woman with EGFR L858R-mutated lung adenocarcinoma (cT1cN3M1c stage IVB) who initiated first-line osimertinib 80 mg/day. Severe hematologic toxicity required sequential dose reductions to 40 mg/day and subsequently 40 mg every other day. Although extracranial disease remained well controlled, the patient developed LMC three months after treatment initiation, accompanied by a rapid rise in carcinoembryonic antigen and sialyl Lewis X levels. Erlotinib 150 mg/day was introduced based on reports of dose‑dependent CNS efficacy, resulting in prompt improvement of neurological symptoms; however, grade 3 thrombocytopenia led to treatment interruption, followed by rapid neurological decline and death. This case illustrates that reduced‑dose EGFR TKI therapy, even with a CNS‑penetrant agent such as osimertinib, may provide insufficient cerebrospinal fluid drug exposure to prevent CNS progression. Clinicians should recognize that dose modification necessitated by adverse events may compromise CNS control, and vigilant monitoring for neurological symptoms is essential in patients receiving reduced‑dose EGFR TKIs.