Isolated Hepatic Perfusion With Melphalan Improves PFS, ORR for Patients With Isolated Uveal Melanoma Liver Metastases

A one-time treatment with isolated hepatic perfusion (IHP) with melphalan improved median progression-free survival (PFS) compared with best alternative treatment for patients with previously untreated isolated liver metastases from uveal melanoma, according to findings from the phase 3 SCANDIUM trial (NCT04463368) published in the Journal of Clinical Oncology.

Findings showed that the median PFS was 7.4 months (95% CI, 5.2-11.6) in the IHP cohort (n = 43) compared with 3.3 months (95% CI, 2.9-3.7) for those in the control group (n = 44; HR, 0.21; 95% CI, 0.12-0.36; P < .0001). The median hepatic PFS was 9.1 months (95% CI, 2.9-4.0) vs 3.3 months (95% CI, 2.9-4.0) favoring the IHP arm (HR, 0.21; 95% CI, 0.12-0.36; P < .0001). (TABLE 1)

The estimated 6-month PFS was 58% in the IHP group vs 8% in the control group.

“The present randomized controlled trial shows that a 1-time treatment with IHP results in significantly superior antitumor responses and PFS compared with treatment with chemotherapy or immune checkpoint inhibitors in treatment-naïve patients with isolated liver metastases of uveal melanoma,” wrote lead study author Roger Olofsson Bagge, MD, PhD, and colleagues. “The first analysis of overall survival [OS], the primary end point of the study, is planned for 2023.”

Olofsson Bagge is a professor in Cancer Surgery at the Institute of Clinical Sciences at Sahlgrenska Academy and a senior consultant surgeon at the Sahlgrenska University Hospital in Gothenburg, Sweden.

Uveal melanoma accounts for approximately 3% of all melanomas. Approximately 50% of patients with uveal melanoma will develop metastases, even in cases when the primary tumor is successfully eradicated from the eye with surgery or radiotherapy. Previous results have shown that these metastases are strongly hepatotropic—more than half of patients with metastases developed isolated liver metastases. The median OS is only 10 to 12 months in this population, and only a few patients survive more than 5 years. In general, these patients do not respond well to systemic chemotherapy, and immune checkpoint inhibition has had only limited efficacy.

IHP 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. Findings from a retrospective study showed a 14-month increase in survival for Swedish patients who received IHP.

In this randomized phase 3 SCANDIUM trial, investigators compared IHP with the investigator’s choice of therapy (chemotherapy, 49%; immune checkpoint inhibitors, 39%; locoregional treatment other than IHP, 9%) as first-line treatment for patients with isolated uveal melanoma liver metastases. This preplanned analysis presented results for PFS, hepatic PFS, overall response rate (ORR), and serious adverse effects (SAEs).

Investigators screened 147 patients from July 2013 to March 2021 and enrolled 93 at 6 sites. Forty-six were assigned to IHP and 47 to the control group. Eighty-seven patients were included in the intention-to-treat population.

The median patient age in the IHP group was 65 years (interquartile range [IQR], 58-71) vs 68 years (IQR, 59-73) in control group. Women made up a significantly larger proportion of the IHP cohort (56% vs 36%). The median time since primary diagnosis was 1.72 years (IQR, 1.15-3.56) in the IHP group and 2.48 years (IQR, 1.14-3.51) for control patients.

At the March 2022 data cutoff, the median duration of follow-up for this interim analysis was 18.6 months (range, 1.4-24.0).

Investigators observed an ORR of 40% in the IHP group compared with 4.5% in the control group. (P < .0001). There were 3 (7%) complete responses in the IHP group and none in the control group. (TABLE 2)

The median duration of response was 13.7 months (95% CI, 11.6-18.3) with IHP vs 8.8 months (95% CI, 6.0-not evaluable) in the control group.

Eight patients (19.5%) assigned to IHP experienced SAEs compared with 3 (6.5%) in the control group. All SAEs reported in the IHP group occurred within 3 months of treatment administration.

There was one treatment-related death in the IHP group. A patient who had a liver artery dissection detected 7 days following IHP died 16 days after IHP due to multiorgan failure secondary to liver artery thrombosis causing liver necrosis and aspiration pneumonia.

Reference

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. Published online March 20, 2023. doi:10.1200/JCO.22.01705