TY - JOUR
T1 - Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases
T2 - A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial)
AU - Olofsson Bagge, Roger
AU - Nelson, Axel
AU - Shafazand, Amir
AU - All-Eriksson, Charlotta
AU - Cahlin, Christian
AU - Elander, Nils
AU - Helgadottir, Hildur
AU - Kiilgaard, Jens Folke
AU - Kinhult, Sara
AU - Ljuslinder, Ingrid
AU - Mattsson, Jan
AU - Rizell, Magnus
AU - Sternby Eilard, Malin
AU - Ullenhag, Gustav J
AU - Nilsson, Jonas A
AU - Ny, Lars
AU - Lindnér, Per
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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.
AB - 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.
KW - Chemotherapy, Cancer, Regional Perfusion/adverse effects
KW - Humans
KW - Liver Neoplasms/therapy
KW - Melphalan
KW - Perfusion
KW - Prospective Studies
KW - Scandium/therapeutic use
UR - http://www.scopus.com/inward/record.url?scp=85160458547&partnerID=8YFLogxK
U2 - 10.1200/JCO.22.01705
DO - 10.1200/JCO.22.01705
M3 - Journal article
C2 - 36940407
SN - 0732-183X
VL - 41
SP - 3042
EP - 3050
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 16
ER -