High-Dose Furmonertinib in Patients With EGFR-Mutated NSCLC and Leptomeningeal Metastases: A Prospective Real-World Study

作者：Haiyang Chen, Sen Yang, Lili Wang, Yingxi Wu, Yufeng Wu, Shuxiang Ma, Zhen He, Cuicui Zhang, Yang Liu, Haoran Tang, Hang Dong, Qiming Wang · 发表于：Journal of Thoracic Oncology · 年份：2024 · DOI：10.1016/j.jtho.2024.09.1385 · 被引用次数：39 · 研究领域：Brain Metastases and Treatment、Lung Cancer Treatments and Mutations、Lung Cancer Research Studies

INTRODUCTION: Leptomeningeal metastasis (LM) is one of the most severe complications of NSCLC. Furmonertinib is a pan-EGFR tyrosine kinase inhibitor (TKI) with a high rate of brain penetration and a wide therapeutic window. Here, we evaluated the efficacy and safety of high-dose furmonertinib in patients with EGFR-mutated NSCLC and LM. METHODS: This prospective real-world study included patients with EGFR-mutated NSCLC and LM treated with a high-dose furmonertinib (240 mg once daily) as a monotherapy or in combination with other treatments. The primary end point was overall survival, and the secondary end points included time to treatment discontinuation and clinical response rate. Additional efficacy evaluations included changes in brain magnetic resonance imaging by the response assessment in neuro-oncology-LM radiologic criteria. We also introduced next-generation sequencing-based assays to evaluate genomic and epigenomic features of cell-free DNA (cfDNA) in patients' cerebrospinal fluid (CSF) samples and to analyze their associations with patient outcomes. RESULTS: We enrolled 48 patients, of whom 35 (72.9%) had received third-generation EGFR TKIs. The median overall survival was 8.43 months (95% confidence interval: 5.48-11.39 mo), while the median time to treatment discontinuation was 8.27 months (95% confidence interval: 5.40-11.14 mo), and the clinical response rate was 75%. The LM objective response rate and disease control rate assessed with response assessment in n...