Incidence of leptomeningeal metastasis and prognosis after its development in patients with advanced non-small cell lung cancer: a prospective real-world observational study (CS-Lung-003-linked study 37)

This study was conducted as part of a prospective multicenter observational study (CS-Lung-003) and aimed to investigate the incidence of leptomeningeal metastasis (LM) and prognosis after its development in patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. Data from 1,149 patients with advanced NSCLC were prospectively collected and analyzed to evaluate the incidence and clinical characteristics of LM. LM developed in 37 patients (3.2%) during the overall treatment course. The incidence of LM was 4% (33/801) in patients with adenocarcinoma histology and 6% (23/367) in those with driver gene mutations/fusions, including 6% (17/300) in patients with EGFR mutations and 10% (5/51) in those with ALK fusions. The median overall survival (OS) from LM diagnosis was 5.9 months among the 37 patients. Younger age (<75), the presence of brain metastasis at the time of NSCLC diagnosis, and the presence of driver gene mutations/fusions were identified as independent risk factors for LM development. The systemic anti-tumor therapy after LM diagnosis was significantly associated with improved OS (median OS: 10.9 vs. 1.8 months, HR 0.12, p =0.0097). Tyrosine kinase inhibitors (TKIs) were the most commonly used treatment (n=16), and 15 of these patients received TKI re-administration. Patients treated with TKIs tended to have longer OS (11.6 months) than those who did not receive TKIs (5.9 months). This CS-Lung-003-linked study (study 37) demonstrated that LM developed in 3.2% of patients with advanced NSCLC during the overall treatment course, and that systemic anti-tumor therapy, including TKI re-administration, was associated with improved OS after LM diagnosis.