Leptomeningeal Metastasis in Patients With EGFR-positive NSCLC: A Propensity-matched Retrospective Study of Patients With EGFR-negative NSCLC

Background/Aim:

Although patients with epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) can expect long-term survival, some patients develop leptomeningeal metastasis (LM). The study aimed to clarify whether patients with EGFR-positive NSCLC have a higher incidence of LM than patients with EGFR-negative NSCLC using propensity matching, and to clarify the clinical characteristics of patients with EGFR-positive NSCLC who develop LM.

Patients and Methods:

This retrospective study reviewed the medical records of consecutive patients diagnosed with NSCLC from 2009 to 2025. In addition to common non-parametric tests, we performed propensity matching.

Results:

We evaluated 895 patients with NSCLC, including 185 EGFR-positive patients. The incidence of LM was higher in EGFR-positive patients than in EGFR-negative patients (2.7% vs. 1.4%; p=0.01). Using propensity matching for age, sex, pathological type, and clinical stage, we confirmed the incidence of LM in EGFR-positive patients was higher than in EGFR-negative patients (9.1% vs. 1.2%; p=0.01). In EGFR-positive patients, LM was more likely to develop in younger women, and in those with brain or bone metastases, or pleural or peritoneal dissemination during their clinical courses. Among patients with LM, EGFR-positive patients had a longer time from LM onset to death. Among EGFR-positive patients who developed LM, those who received osimertinib tended to have a longer time to onset of LM and a longer overall survival.

Conclusion:

LM has been attracting attention, possibly due to the long-term survival achieved by EGFR-tyrosine kinase inhibitors. Additional information is required to clarify the risk of LM.