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Isolated Hepatic Perfusion with Melphalan Improves Response Rate and PFS in Previously Untreated Patients with Isolated Liver Metastases from Uveal Melanoma

April 5, 2023

In a first analysis of a randomised controlled phase III study conducted among previously untreated patients with isolated liver metastases from primary uveal melanoma, a single treatment with isolated hepatic perfusion with melphalan was well tolerated with manageable side effects and resulted in significantly higher overall response rate (ORR) and improved progression-free survival (PFS) and hepatic PFS (hPFS) compared with the investigator’s choice of available treatments. The first analysis of overall survival (OS), the primary endpoint of the study, is planned for 2023. The findings from the SCANDIUM study are published by Prof. Roger Olofsson Bagge of the University of Gothenburg and Sahlgrenska University Hospital in Gothenburg, Sweden and colleagues on 20 March 2023 in the Journal of Clinical Oncology.

Uveal melanoma accounts for approximately 3% of all melanomas. Approximately 50% of patients with uveal melanoma develop metastases that are strongly hepatotropic; isolated liver metastases are seen in over half of patients with metastatic disease. Among these patients, the median survival is approximately 10-12 months and only a few patients survive more than 5 years. In contrast to cutaneous melanoma, immune checkpoint inhibitors (ICIs) have been of only limited benefit in patients with uveal melanoma. A recent randomised phase III study of tebentafusp resulted in a significant improvement in OS. For patients with isolated liver metastases, several locoregional liver treatment strategies have been investigated.

Isolated hepatic perfusion with melphalan is a regional treatment where the liver is completely isolated from the systemic circulation to allow hepatic perfusion with high concentrations of chemotherapy, with minimal systemic exposure. In the SCANDIUM, multicentre, randomised, open-label, phase III study, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive an one-time treatment with isolated hepatic perfusion with melphalan or best alternative care. The primary endpoint was OS at 24 months. In the latest article published in the JCO, they reported the secondary outcomes of ORR according to RECIST v1.1 criteria, PFS, hPFS, and safety.

A total, 93 patients were included; 43 patients were assigned to isolated hepatic perfusion and 44 patients to the investigator’s choice of treatment (control group). In the control group, 49% received chemotherapy, 39% ICIs, and 9% locoregional treatment other than isolated hepatic perfusion. In an intention-to-treat analysis, the ORRs were 40% versus 4.5% in the isolated hepatic perfusion and control groups (p < 0.0001). The median PFS was 7.4 months versus 3.3 months (hazard ratio 0.21, 95% confidence interval [CI] 0.12 to 0.36; p < 0.0001), and the median hPFS was 9.1 months versus 3.3 months (p < 0.0001), both favouring the isolated hepatic perfusion group.

There were 11 treatment-related serious adverse events in the isolated hepatic perfusion group compared with 7 in the control group. There was one treatment-related death in the isolated hepatic perfusion group.

The authors commented that the outcomes in the control group were similar to those reported in other recent studies, confirming that the control group is representative, and there was no cross-over allowing for isolated hepatic perfusion in the control group. The recent approval of tebentafusp for the treatment of patients with HLA-A*02:01 subtype uveal melanoma is a major advance. However, no patients in the control group received tebentafusp as the treatment was not available during the inclusion phase of the study.

An interesting development is the combination of isolated hepatic perfusion or percutaneous hepatic perfusion with systemic immunotherapy. Data have shown a correlation between OS and a high infiltration of CD8-positive T cells in metastases and an activated immune cell profile in peripheral blood in patients treated with isolated hepatic perfusion, and ongoing studies are currently investigating the combination of CTLA-4 and PD-1 inhibitors with either percutaneous hepatic perfusion (CHOPIN study) or isolated hepatic perfusion (SCANDIUM-II study).

The study findings were previously presented at the ASCO 2022 Annual Meeting (3-7 June 2022, Chicago, IL, US).

The study was supported by grants from the Signe and Olof Wallenius Foundation, The Assar Gabrielsson Foundation, Gothenburg Society of Medicine, Wilhelm and Martina Lundgrens Foundation, The Erling-Persson Foundation, Knut and Alice Wallenberg Foundation, The Swedish Cancer Society, and The Swedish Research Council.