期刊
BMC MEDICINE
卷 20, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12916-022-02387-0
关键词
Cerebrospinal fluid; Leptomeningeal metastases; Osimertinib
资金
- Project of National Natural Science Foundation [81802298]
- Key Lab System Project of Guangdong Science and Technology Department -Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer [2017B030314120]
- Guangdong Provincial People's Hospital Young Talent Project [KY012021191]
- High-level Hospital Construction Project [DFJH201910]
This study revealed site-specific resistant mechanisms to osimertinib and investigated subsequent treatments for leptomeningeal metastases (LM) in EGFR-mutated NSCLC patients. Private resistant mechanisms in cerebrospinal fluid (CSF) might match osimertinib-resistant LM for targeted therapy. Continuing osimertinib with intensification strategy might prolong survival, especially for those with CNS-only progression.
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.
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