Efficacy and Safety of Intraventricular Thiotepa in Combination With Methotrexate for Leptomeningeal Metastasis From Breast Cancer (NJMU-BC04): A Single-Arm Phase II Study.

Leptomeningeal metastasis (LM), an uncommon yet highly fatal condition, involves malignant tumor infiltration of the meninges resulting in progressive neurological deterioration and severe quality-of-life impairment. LM remains largely refractory to treatment and lacks standardized treatment consensus, with a low intracranial objective response rate (iORR) of 20% and a short median intracranial progression-free survival (iPFS) of 2.2 months. In this study, adult patients with breast cancer-related LM received intraventricular thiotepa combined with methotrexate. The primary endpoint was achieved with an iORR of 45.8% (11 out of 24, 95% CI: 25.55-67.18%), and the intracranial disease control rate was 58.3% (14 out of 24, 95% CI: 36.64-77.89%). From treatment initiation, the median iPFS and overall survival were 7.9 months (95% CI: 5.3-not estimable) and 11.7 months (95% CI: 5.7-not estimable), respectively. Grade 3-4 treatment-related adverse events occurred in 62.5% (15 out of 24) of patients, most commonly thrombocytopenia (37.5%) and leukopenia (33.3%), with no Grade 5 toxicities. The exploratory study indicated that two proteins in CSF and four plasma proteins were significantly associated with iORR. Overall, the regimen was feasible and demonstrated a manageable safety profile, with a preliminary signal of clinical benefit warranting further investigation.