2025/07/01 by Zager, Jonathan, Orloff, Marlana, Ferrucci, Pier Francesco +23
Biochemistry, Genetics and Molecular Biology · Medicine · #610 Medicine & #Brain Metastases and Treatment #Liver-directed therapy #Melphalan/Hepatic Delivery System #Metastatic uveal melanoma #Microtubule and mitosis dynamics #Ocular Oncology and Treatments #Ocular melanoma #Percutaneous hepatic perfusion #health
paper · doi:10.5167/uzh-280262
openalex publication_date 2025/07/01 · openalex created_date 2025/11/23 · openalex updated_date 2026/07/28
Background: Metastatic uveal melanoma (mUM) has a poor prognosis, with liver metastases typically presenting a therapeutic challenge. Melphalan/Hepatic Delivery System (Melphalan/HDS) is a drug/medical device combination used for liver-directed treatment of unresectable mUM patients. This study assessed efficacy and safety of Melphalan/HDS versus best alternative care (BAC). Methods: Eligible patients with unresectable mUM were randomized (1:1) to receive Melphalan/HDS (3 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of 6 cycles or BAC. Due to slow enrollment and patient reluctance to receive BAC treatment, the study design was amended to a single-arm Melphalan/HDS study, and all efficacy analyses of the randomized study were treated as exploratory. Results: The study enrolled 85 patients. Eligible patients were randomized to receive Melphalan/HDS (n = 43) or BAC (n = 42), and 72 patients received study treatment (Melphalan/HDS [n = 40]; BAC [n = 32]). Exploratory analyses of efficacy endpoints showed numerical differences consistently favoring the Melphalan/HDS arm versus BAC (median overall survival: 18.5 vs. 14.5 months; median progression-free survival: 9.1 vs. 3.3 months; objective response rate: 27.5% vs. 9.4%; and disease control rate: 80.0% vs. 46.9%). Serious adverse events (SAEs) occurred in 51.2% of Melphalan/HDS and in 21.9% of BAC patients. The most common (>5%) SAEs included thrombocytopenia (19.5%), neutropenia (9.8%), leukopenia (9.8%) and febrile neutropenia (7.3%) in Melphalan/HDS patients and cholecystitis, nausea and vomiting (6.3% each) in BAC patients. No treatment-related deaths were observed. Conclusion: Treatment with Melphalan/HDS shows clinically meaningful efficacy and demonstrates a favorable benefit-risk profile in patients with unresectable mUM as compared to BAC.