Isolated Hepatic Perfusion More Effective Than Standard Treatments For Patients With Isolated Liver Metastases From Uveal Melanoma
Generally, about half of patients with metastatic uveal melanoma present with isolated liver metastasis.1 The median survival for this rare but fatal symptom of disease is around 1 year, and few treatment options are available to extend the duration of survival.2
Researchers have previously investigated an advanced surgical therapy, isolated hepatic perfusion (IHP) with melphalan, as a treatment option for patients with liver metastases derived from several different types of diseases. This is because IHP is a regional treatment where the liver is completely isolated from the systemic circulation, which allows for hepatic perfusion with high concentrations of chemotherapy.
Therefore, Bagge and colleagues developed a multicenter, randomized, open-label, phase 3 trial that compared IHP and melphalan with first-line treatment options in patients with isolated uveal melanoma liver metastases. The researchers compared overall response rate (ORR), hepatic progression-free survival (hPFS), progression-free survival (PFS), and serious adverse events.3
A total of 93 patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group where patients received the investigator's choice of first-line treatment (n = 44). In the control group, 49% received chemotherapy, 39% received immune checkpoint inhibitors (ICI), and 9% received locoregional treatment other than IHP.
Looking at the primary endpoints, the IHP group had an ORR of 40% vs 4.5% in the control group (P < .0001). The median PFS for the IHP group was 7.4 months vs 3.3 months in the control group (hazard ratio [HR] = 0.21 [95% CI, 0.12 to 0.36]); P < .0001. The median hPFS was 9.1 months in the IHP group vs 3.3 months for the control group (P < .0001). Regarding serious adverse events, there were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group, and there was one treatment-related death in the IHP group.
There were limitations to this study. For example, the authors noted that the control group was treated heterogeneously. Additionally, the researchers pointed to the fact that the study is underpowered for any direct comparison between the individual treatments. Still, the authors believe the study results are notable.
“The present randomized controlled trial shows that a one-time treatment with IHP results in significantly superior antitumor responses and PFS compared with treatment with chemotherapy or ICIs in treatment-naïve patients with isolated liver metastases of uveal melanoma,” the researchers concluded.
References:
- Grossniklaus HE. Progression of ocular melanoma metastasis to the liver: the 2012 Zimmerman lecture. JAMA Ophthalmol. 2013;131(4):462-469. doi:10.1001/10.1200/JCO.22.01705.jamaophthalmol.2013.2547.
- Rantala ES, Kivelä TT, Hernberg MM. Impact of staging on survival outcomes: a nationwide real-world cohort study of metastatic uveal melanoma. Melanoma Res. 2021;31(3):224-231. doi:10.1097/CMR.0000000000000728.
- Olofsson Bagge R, Nelson A, Shafazand A, et al. Isolated hepatic perfusion with melphalan for patients with isolated uveal melanoma liver metastases: a multicenter, randomized, open-label, phase iii trial (the SCANDIUM Trial). J Clin Oncol. 2023;JCO2201705. doi: