Abstract
BACKGROUND
Intra-cerebrospinal fluid (CSF) therapy for the treatment of leptomeningeal metastasis (LM). remains controversial.
METHODS
DEPOSEIN (NCT01645839) was a multicenter randomized open-label study exploring the efficacy of liposomal cytarabine added to standard-of-care systemic therapy for the treatment of LM from breast cancer. Inclusion was based on the identification of tumor cells in the CSF or typical clinical and magnetic resonance imaging (MRI) signs of LM. Patients were randomly assigned to receive systemic therapy alone (arm A) or in combination with intra-CSF liposomal cytarabine (arm B). Neurological and patient-reported outcomes (PRO) were performed monthly, cerebrospinal MRI every 2 months. The primary endpoint was progression-free survival in the leptomeningeal compartment (LM-PFS); 66 events were required to ensure 80% power for a hazard ratio of 0.5 (two-sided alpha=5%).
RESULTS
Thirty-seven patients were assigned to arm A, 36 patients to arm B. Baseline characteristics were similar between arms. The median number of liposomal cytarabine injections in arm B was 5 (range 1–20). Focal radiotherapy was performed in 6 (16%) and 5 (14%) patients in arms A and B, respectively. Serious adverse events were reported in 20 and 27 patients in arms A and B. In the intent-to-treat population, median LM-PFS locally assessed was 2.0 months (95% confidence interval (CI) 1.3 2.7) in arm A versus 4.3 months (95% CI 2.3 5.7) in arm B (HR=0.57, 95% CI 0.35 0.92, p=0.02). Sixty-eight patients have died. Median OS was 4.0 months (95% CI 2.2–6.5) in arm A versus 7.3 months (95%CI 3.9–12.6) in arm B (HR=0.80, 95% CI 0.50–1.29, p=0.35). Centrally reviewed LM-PFS and PRO will also be reported. CONCLUSIONS: The addition of liposomal cytarabine to systemic therapy may improve LM-related PFS but may not significantly improve survival. PRO will be essential to determine a possible clinical benefit from intrathecal chemotherapy.