1. Intrathecal liposomal cytarabine plus systemic therapy versus systemic chemotherapy alone for newly diagnosed leptomeningeal metastasis from breast cancer
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Thomas Boulanger, Jérôme Barrière, Audrey Mailliez, Michael Weller, Emilie Le Rhun, Isabelle Rodrigues, Veronique Lorgis, Yves Marie Robin, Jacques Bonneterre, Marie-Cécile Le Deley, Jennifer Wallet, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, University hospital of Zurich [Zurich], Universität Zürich [Zürich] = University of Zurich (UZH), Service de neuro-oncologie, de neurochirurgie générale et stéréotaxique [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Biostatistiques [CHRU Lille], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département d'Imagerie [Lille] (Cancer Oscar Lambret ), Cancer Oscar Lambret [Lille], Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Département Oncologie Médicale [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service de pathologie [CHU Lille], Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE)-UNICANCER, Service de biostatistiques [CHU Lille] (Centre Oscar Lambret), Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER, University of Zurich, and SALZET, Michel
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Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,brain ,[SDV]Life Sciences [q-bio] ,Population ,Clinical Investigations ,610 Medicine & health ,Breast Neoplasms ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,depocyte ,medicine ,Clinical endpoint ,Humans ,cerebrospinal ,Progression-free survival ,education ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,business.industry ,Hazard ratio ,Cytarabine ,meningitis ,neoplastic ,medicine.disease ,Chemotherapy regimen ,10040 Clinic for Neurology ,3. Good health ,[SDV] Life Sciences [q-bio] ,Radiation therapy ,Oncology ,030220 oncology & carcinogenesis ,Drug Therapy, Combination ,Neurology (clinical) ,business ,medicine.drug - Abstract
Background DEPOSEIN (NCT01645839) was a randomized open-label phase III study to explore the role of intrathecal chemotherapy in patients with newly diagnosed leptomeningeal metastasis (LM), a common manifestation of breast cancer. Methods Patients with newly diagnosed LM defined by tumor cells in the cerebrospinal fluid or combination of clinical and neuroimaging signs of LM were randomized to receive systemic therapy alone (control group) or systemic therapy plus intrathecal liposomal cytarabine (experimental group). Progression-free survival related to LM (LM-PFS) was the primary endpoint. Results Thirty-seven and 36 patients were assigned to the control and the experimental groups. Median number of liposomal cytarabine injections in the experimental group was 5 (range 1–20). Focal radiotherapy was performed in 6 (16%) and 3 (8%) patients in the control and experimental groups. In the intent-to-treat population, median LM-PFS was 2.2 months (95% CI: 1.3–3.1) in the control versus 3.8 months (95% CI: 2.3–6.8) in the experimental group (hazard ratio 0.61, 95% CI: 0.38–0.98) (P = 0.04). Seventy-one patients have died. Median overall survival was 4.0 months (95% CI: 2.2–6.3) in the control versus 7.3 months (95% CI: 3.9–9.6) in the experimental group (hazard ratio 0.85, 95% CI: 0.53–1.36) (P = 0.51). Serious adverse events were reported in 22 and 30 patients, respectively. Quality of life until progression did not differ between groups. Conclusion The addition of intrathecal liposomal cytarabine to systemic treatment improves LM-related PFS. Confirmatory trials with optimized patient selection criteria and more active drugs may be required to demonstrate a survival benefit from intrathecal pharmacotherapy.
- Published
- 2020
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