Melphalan/hepatic delivery system versus best available care in patients with unresectable metastatic uveal melanoma: Randomized FOCUS trial results.

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 .