MMDA-01 LEPTOMENINGEAL DISEASE IN ALK-POSITIVE NSCLC: SURVIVAL IMPACT OF THIRD-GENERATION ALK INHIBITORS

作者：Kelsey Pan, Meimei Zheng, Yang Xia, Aaron Tan, Fangdi Sun, Maxime Borgeaud, Surbhi Singhal, Lingzhi Hong, Jianjun Zhang, Wen Li, Jonathan Riess, John Heymach, Nathaniel Myall, Alfredo Addeo, Daniel Tan, Yilong Wu, Xiuning Le · 发表于：Neuro-Oncology Advances · 年份：2026 · DOI：10.1093/noajnl/vdag161.032 · 研究领域：Lung Cancer Treatments and Mutations、Brain Metastases and Treatment、Lung Cancer Research Studies

Abstract As survival improves for patients with ALK-positive non–small cell lung cancer (NSCLC) treated with successive generations of ALK tyrosine kinase inhibitors (TKIs), leptomeningeal disease (LMD) has emerged as a critical unmet need. Although next-generation ALK TKIs were designed to enhance central nervous system (CNS) penetration and control parenchymal brain metastases, their efficacy in LMD remains less well defined, and data regarding radiation, anti-angiogenic agents, and intrathecal therapies are limited. We conducted a global, multi-center retrospective analysis of 141 patients with ALK-positive NSCLC and radiographically and/or cytologically confirmed LMD treated between 2007 and 2024 across five academic centers in the United States and Asia. Baseline demographic, clinical, and treatment data were collected, and subgroup and multivariable analyses evaluated associations with leptomeningeal overall survival (LMOS). Among patients, 79.4% had radiographic LMD, 41.1% had positive CSF cytology, and 59.6% were symptomatic. Median time from metastatic diagnosis to LMD was 40.6 months in patients previously treated with a third-generation (3G) ALK TKI versus 23.7 months in those without prior 3G exposure (p < 0.001). Median LMOS was 22.5 months. In treatment-naïve patients, LMOS was 42.4 months with second-generation (2G) TKI alone, 49.6 months with escalation from 2G to 3G TKI, and not reached with upfront 3G TKI (p < 0.001). Among patients previously ...