Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases: A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial)

Abstract

PURPOSE About half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking. METHODS In this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety. RESULTS Ninety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively ( P < .0001). The median PFS was 7.4 months versus 3.3 months ( P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months ( P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group. CONCLUSION IHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.

Updates in the Management of Uveal Melanoma

“…Other hepatic artery–based methods include isolated hepatic infusion (IHP), which is a more invasive procedure than PHP, and hepatic artery infusion (HAI) therapies. In the randomized SCANDIUM trial, IHP with melphalan led to a significantly improved response rate (RR) and PFS than investigator choice therapy 84 . Although OS was numerically superior for IHP at 2 years, it did not reach statistical significance 84 .…”

“…In the randomized SCANDIUM trial, IHP with melphalan led to a significantly improved response rate (RR) and PFS than investigator choice therapy 84 . Although OS was numerically superior for IHP at 2 years, it did not reach statistical significance 84 . The EORTC 18021 trial compared fotemustine-HAI with intravenous fotemustine and, as with the SCANDIUM trial, demonstrated an improved RR without a survival benefit 85 …”

Management of Uveal Melanoma: Updated Cancer Care Alberta Clinical Practice Guideline

“…There have been several liver-directed therapies that have been investigated in the metastatic uveal setting, both randomized and nonrandomized. The two randomized studies, FOCUS and SCANDIUM, utilized intrahepatic melphalan as the intervention and both demonstrated statistically significant improvements in PFS and overall response rate (ORR) as compared to best alternative care [122,123]. However, the OS data on these studies are still pending and these invasive procedures are typically only available at specialized tertiary cancer centres.…”

DSE inhibits melanoma progression by regulating tumor immune cell infiltration and VCAN

“…If diagnosed at this early stage, local lesions can be successfully removed with surgery. However, melanoma can rapidly transition to a vertical growth stage, in which it invades the dermis and then metastasizes to lymph and distant organs such as the lungs [ 7 , 8 ], liver [ 9 ] and brain [ 10 ](stage III and IV, respectively), and these later stages are associated with a sharp decline in median 5-year survival [ 11 ]. Therefore, it is necessary to explore the molecular mechanisms that lead to melanoma development and metastasis, and to discover other therapeutic targets and biomarkers to improve patient survival.…”