A phase III trial has shed light on a promising liver-directed treatment for patients with unresectable metastatic uveal melanoma (mUM). The FOCUS trial compared the efficacy and safety of Melphalan/Hepatic Delivery System (Melphalan/HDS) with best alternative care (BAC) in patients whose cancer had spread to the liver.
Uveal melanoma (UM) accounts for only 3-5 percent of all melanoma cases, but up to 50 percent of UM patients will develop metastatic disease (mUM), with 90 percent of these patients then developing liver involvement. This makes liver-directed therapies an appealing strategy. Melphalan/HDS, a minimally invasive percutaneous hepatic perfusion (PHP) approach, delivers high-dose chemotherapy directly to the liver while filtering the blood to minimize systemic exposure.
The randomized study initially enrolled 85 patients but was later amended to a single-arm trial due to slow enrollment and reluctance toward BAC. Exploratory analyses showed that Melphalan/HDS improved clinical outcomes compared to BAC.
Although serious adverse events were more frequent with Melphalan/HDS (notably hematologic toxicities, such as thrombocytopenia and neutropenia), these were largely manageable and transient, and no treatment-related deaths occurred during the trial.
The trial reinforces Melphalan/HDS (marketed as HEPZATO KIT in the US) as a viable FDA-approved option for patients with unresectable mUM. With the emergence of combination therapies (e.g., Melphalan/HDS plus immune checkpoint inhibitors) under investigation, the study marks a critical advance in the fight against this rare and difficult-to-treat cancer.
