Survival and Quality of Life after Isolated Hepatic Perfusion with Melphalan as a Treatment for Uveal Melanoma Liver Metastases - Final Results from the Phase III Randomized Controlled Trial SCANDIUM

Roger Olofsson Bagge; Axel Nelson; Amir Shafazand; Charlotta All-Eriksson; Christian Cahlin; Nils Elander; Anders Gustavsson; Hildur Helgadottir; Jens Folke Kiilgaard; Sara Kinhult; Ingrid Ljuslinder; Jan Mattsson; Magnus Rizell; Malin Sternby Eilard; Gustav J Ullenhag; Jonas A Nilsson; Lars Ny; Per Lindnér

doi:10.1097/SLA.0000000000006255

Survival and Quality of Life after Isolated Hepatic Perfusion with Melphalan as a Treatment for Uveal Melanoma Liver Metastases - Final Results from the Phase III Randomized Controlled Trial SCANDIUM

Ann Surg. 2024 Feb 29. doi: 10.1097/SLA.0000000000006255. Online ahead of print.

Authors

Roger Olofsson Bagge^{1

2

3}, Axel Nelson⁴, Amir Shafazand^{3

5}, Charlotta All-Eriksson⁶, Christian Cahlin⁷, Nils Elander⁸, Anders Gustavsson^{9

10}, Hildur Helgadottir¹¹, Jens Folke Kiilgaard¹², Sara Kinhult¹³, Ingrid Ljuslinder¹⁴, Jan Mattsson², Magnus Rizell⁷, Malin Sternby Eilard⁷, Gustav J Ullenhag^{15

16}, Jonas A Nilsson^{1

17}, Lars Ny⁴, Per Lindnér⁷

Affiliations

¹ Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
³ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁴ Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁵ Department of Radiology, Alingsås Hospital, Alingsås, Sweden.
⁶ Department of Ophthalmology, Mölndal Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁷ Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁸ Department of Oncology and Department of Clinical and Biomedical Sciences, Linköping University, Linköping, Sweden.
⁹ Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Solna, Sweden.
¹⁰ Quantify Research, Stockholm, Sweden.
¹¹ Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
¹² Department of Ophthalmology, Rigshospitalet, Copenhagen University Hospital Copenhagen, Denmark.
¹³ Department of Oncology, Skåne University Hospital, Lund, Sweden.
¹⁴ Department of Oncology, Norrlands University Hospital, Umeå, Sweden.
¹⁵ Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratories, Uppsala University, Uppsala, Sweden.
¹⁶ Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
¹⁷ Harry Perkins Institute of Medical Research, University of Western Australia, Perth, WA, Australia.

PMID: 38420778
DOI: 10.1097/SLA.0000000000006255

Abstract

Objective: To investigate overall survival (OS) and health-related quality of life (HRQOL) of first-line isolated hepatic perfusion (IHP) compared to best alternative care (BAC) for patients with uveal melanoma liver metastases.

Summary background data: Approximately half of patients with uveal melanoma develop metastatic disease, most commonly in the liver and systemic treatment options are limited. Isolated hepatic perfusion (IHP) is a locoregional therapy with high response rates but with unclear effect on overall survival (OS).

Methods: In this phase III randomized controlled multicenter trial (the SCANDIUM trial) patients with previously untreated isolated uveal melanoma liver metastases were included between 2013-2021, with at least 24 months of follow-up. The planned accrual was 90 patients randomized 1:1 to receive a one-time treatment with IHP or BAC. Crossover to IHP was not allowed. The primary endpoint was the 24-month OS rate, with the hypothesis of a treatment effect leading to a 50% OS rate in the IHP group compared to 20% in the control group. HRQOL was measured by the EuroQol 5-domains 3-levels (EQ-5D-3L) questionnaire over 12 months.

Results: The intention-to-treat (ITT) population included 87 patients randomized to the IHP group (43 patients; 41 [89%] received IHP) or the control group (44 patients). The control group received chemotherapy (49%), immunotherapy (39%), or localized interventions (9%). In the ITT population, the median PFS was 7.4 months in the IHP group compared with 3.3 months in the control group, with a hazard ratio of 0.21 (95% CI, 0.12-0.36). The 24-month OS rate was 46.5% in the IHP group versus 29.5% in the control group (P=0.12). The median OS was 21.7 months versus 17.6 months, with a hazard ratio of 0.64 (95% CI, 0.37-1.10). EQ-5D-3L showed a sustained high health status for the IHP group over 12 months, compared to a deteriorating trend in the control group.

Conclusions: For patients with liver metastases from uveal melanoma, IHP offers high response rates translating to a benefit in PFS including a trend of better HRQOL compared to the control group. However, the primary endpoint of OS at 24 months was not met.