Prolonged Survival in HER2 Mutant Metastatic NSCLC with Leptomeningeal Metastases Treated with Intrathecal Trastuzumab and Methotrexate: A Case Report

Abstract Leptomeningeal metastasis (LM) is a devastating complication of any solid organ malignancy, including nonsmall cell lung cancer (NSCLC). Human Epidermal Growth Factor Receptor2 HER2 mutant NSCLC is a rare subtype detected in only 2 to 4% cases. The occurrence of LM in HER2 mutant NSCLC is an extremely rare event. This case report describes a HER2 mutant NSCLC patient who developed LM during treatment with maintenance intravenous (IV) pemetrexed 500 mg/m2 following four cycles of pemetrexed 500 mg/m2 and carboplatin area under the curve 5. He was treated with a combination of twice-weekly intrathecal (IT) methotrexate (12.5 mg), trastuzumab (75 mg), and hydrocortisone (50 mg) with continued 3-weekly maintenance IV Pemetrexed. Patient improved clinically after the first week of initiation of IT therapy. Cerebrospinal fluid (CSF) was negative for malignant cells after seven doses of IT therapy, after which IT therapy was switched to once weekly. After 3 months, IT therapy was continued at 3 weekly intervals with IV Pemetrexed. Patient is still progression-free after 12 months of initiation of IT therapy. Toxicities were minimal and conservatively manageable. This is the first reported case of HER2 mutant NSCLC with LM treated with IT trastuzumab, methotrexate, and hydrocortisone, along with maintenance IV chemotherapy, and the patient has remained progression-free after 12 months of initiation of IT therapy. This regimen can be considered as a novel treatment of choice for HER2 mutant NSCLC with LM, especially in resource limited setting.