Overcoming refractory leptomeningeal metastasis in nonsmall cell lung cancer with intrathecal pemetrexed and osimertinib: a case report.

Leptomeningeal metastasis (LM), a devastating complication of advanced nonsmall cell lung cancer (NSCLC), severely compromises patient survival and quality of life. Currently, standardized diagnostic criteria and treatment protocols for NSCLC-associated LM remain undefined, posing significant clinical challenges. Here, we present a case of a 58-year-old female with advanced epidermal growth factor receptor (EGFR)-mutated (exon 19 deletion) lung adenocarcinoma who developed LM after failing first-line gefitinib therapy. Initial treatment with osimertinib (80 mg/day), a third-generation EGFR-tyrosine kinase inhibitor (TKI), achieved 8 months of disease control before LM progression. Cerebrospinal fluid genomic analysis revealed acquired EGFR mutations (exon19 L747-A750delins and exon18 L718Q). Combination therapy with intrathecal pemetrexed and standard-dose osimertinib temporarily alleviated neurological symptoms. Upon disease recurrence after 6 months, therapeutic intensification through increased intrathecal pemetrexed frequency and high-dose osimertinib (160 mg/day) resulted in sustained neurological improvement and prolonged survival with manageable toxicity. This case demonstrates the potential of optimized intrathecal/systemic TKI combination strategies for EGFR-mutant NSCLC with LM, providing clinical insights for this therapeutic dilemma.