Melphalan/hepatic delivery system versus best available care in patients with unresectable metastatic uveal melanoma: Randomized FOCUS trial results.
Year: 2024
Type: conference-abstract
Abstract: 9556 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. The purpose of the FOCUS study, an open label, multicenter randomized Phase 3 study, was to assess efficacy and safety of melphalan/HDS versus best alternative care (BAC). Methods: Eligible patients with unresectable mUM were randomized 1:1 to treatment with melphalan/HDS (3.0 mg/kg ideal body weight) once every 6-8 weeks for a maximum of 6 cycles or BAC. The primary endpoint was overall survival (OS). The planned study size was 240 patients; 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: From February 2016 to October 2018 a total of 129 patients were screened and 85 were enrolled at 22 centers in the US and Europe; eligible patients were randomized to receive melphalan/HDS (N=43) or BAC (N=42) and 72 patients received study treatment. Exploratory analyses of efficacy endpoints showed numerical differences consistently favoring the melphalan/HDS arm vs. BAC (median OS: 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. Most common (>5%) SAEs included thrombocytopenia (19.5%), and 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. Conclusions: Treatment with melphalan/HDS shows clinically meaningful efficacy and demonstrates a favorable benefit-risk profile in patients with unresectable mUM as compared to best alternative care. Clinical trial information: NCT02678572 .
Source: Journal of Clinical Oncology
Authors: Jonathan S. Zager, Marlana M. Orloff, Pier Francesco Ferrucci, Junsung Choi, David J. Eschelman, Evan Scott Glazer, Aslam Ejaz, Erika Richtig, Sebastian Ochsenreither, Sunil A. Reddy, Michael C. Lowe, Georgia Beasley, Anja Heike Gesierich, Martin Gschnell, Reinhard Dummer, Ana Maria Arance, Stephen William Fenwick, Johnny John, Matthew Wheater, Christian H.H Ottensmeier, FOCUS Trial Authors
Institutions: Moffitt Cancer Center, Thomas Jefferson University, Sidney Kimmel Cancer Center, MultiMedica, University of Tennessee Health Science Center, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Medical University of Graz, Charité – Universitätsmedizin Berlin, Stanford University, Emory University, Duke University, Universitätsklinikum Würzburg, Universitätsklinikum Gießen und Marburg, University Hospital Zurich, Hospital Clínic de Barcelona, Liverpool University Hospitals NHS Foundation Trust, Delcath Systems (United States), University Hospital Southampton NHS Foundation Trust, University of Southampton, University of Liverpool
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4400272363