Subsequent treatments beyond progression on osimertinib in EGFR-mutated NSCLC and leptomeningeal metastases

作者：Mei-Mei Zheng, Yang-Si Li, Hai‐Yan Tu, Hao Sun, Kai Yin, Ben‐Yuan Jiang, Jin‐Ji Yang, Xu‐Chao Zhang, Qing Zhou, Chong‐Rui Xu, Zhen Wang, Hua‐Jun Chen, Dexiang Zhou, Yi‐Long Wu · 发表于：BMC Medicine · 年份：2022 · DOI：10.1186/s12916-022-02387-0 · 被引用次数：12 · 研究领域：Lung Cancer Treatments and Mutations、Brain Metastases and Treatment、Lung Cancer Research Studies

BACKGROUND: Despite the reported efficacy of osimertinib, central nervous system (CNS) progression is still frequent in EGFR-mutated NSCLC. This study aimed to reveal site-specific resistant mechanisms to osimertinib and investigate subsequent treatments for leptomeningeal metastases (LM). METHODS: EGFR-mutated NSCLC with LM who progressed on osimertinib were included. Molecular analysis of cerebrospinal fluid (CSF) at osimertinib progression was performed. Subsequent treatments of LM were collected and analyzed. RESULTS: A total of 246 patients were identified. Only those with LM as a progression site on osimertinib were included (n=81). In 58 CSF-plasma pairs, more alterations were uniquely detected in CSF (77%) than in plasma (7%). These mechanisms led to 22 patients receiving matched targeted therapy. Among them, 16 (72.7%) had a clinical response. The median overall survival was 7.2 months. For non-matched therapy (n=59), the osimertinib combination had a longer median overall survival than the regimen switch in CNS-only progression (15.3 vs. 7 months, p=0.03). Finally, serial monitoring by CSF revealed the potential evolution of LM. CONCLUSIONS: Private resistant mechanisms in CSF might match osimertinib-resistant LM for targeted therapy. Besides, continuing osimertinib with intensification strategy might prolong survival, especially for those with CNS-only progression. Prospective exploration is needed.