Isolated Hepatic Perfusion Yields Responses in Melanoma Liver Metastases

The use of isolated hepatic perfusion significantly improved efficacy outcomes including overall response rate (ORR) in patients with isolated uveal melanoma liver metastases compared with the use of best alternative care, according to published findings from the phase 3 SCANDIUM trial (NCT01785316).

“In summary, the present randomized controlled trial shows that a one-time treatment with [isolated hepatic perfusion] 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,” according to the study authors.

In the trial, the ORR was 40% for patients receiving isolated hepatic perfusion vs 4.5% for those receiving control treatment (P <.0001). Additionally, the disease control rate (DCR) in each respective group was 58% vs 15%.

The estimated progression-free survival (PFS) rates at 6 months were 58% in the isolated hepatic perfusion group vs 8% in the control group. The median PFS was 7.4 months (95% CI, 5.2-11.6) vs 3.3 months (95% CI, 2.9-3.7) in each respective group (Hazard ratio [HR], 0.21; 95% CI, 0.12-0.36; P <.0001). In the control group, the median PFS was 3.0 months for those receiving chemotherapy compared with 3.3 months for those receiving immune checkpoint inhibitors [ICIs].

“In summary, the present randomized controlled trial shows that a one-time treatment with [isolated hepatic perfusion] 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 study investigators stated. “The first analysis of overall survival [OS], the primary end point of the study, is planned for 2023.”

Investigators of the prospective, multi-center, open-label phase 3 SCANDIUM trial randomly assigned patients 1:1 to receive isolated hepatic perfusion or investigator’s choice of treatment. Isolated hepatic perfusion involved a target flow rate of 500 to 1200 mL/min with a target liver temperature of 40°C along with melphalan at a dose of 1 mg/kg body weight divided into 2 doses administered 30 minutes apart. Patients in the isolated hepatic perfusion group were not permitted to receive any other anti-tumor treatment during follow-up until disease progression.

The primary end point was the 24-month OS rate. Secondary end points included ORR, hepatic PFS, serious adverse effects (SAEs), PFS, and duration of response (DOR).

Patients who had histologically or cytologically confirmed liver metastases from uveal melanoma and measurable disease per RECIST v1.1 criteria were eligible for enrollment. Patients were also eligible if they had received no previous therapy for melanoma metastases and had no evidence of extrahepatic disease by PET-CT.

Between July 2013 and March 2021, investigators randomly assigned 87 patients across 6 treatment sites, including 43 patients in the isolated hepatic perfusion group and 44 in the control group. The median patient age was 65 years (range, 27-80) in the isolated hepatic perfusion group and 68 years (range, 40-85) in the control group. The median duration of follow-up at the time of data cutoff was 18.6 months (range, 1.4-24.0). Most patients in the isolated hepatic perfusion group were female (56%), and most in the control group were male (64%).

The median operating time was 5.0 hours (range, 1.0-8.0), and the median hospital stay was 7 days (range, 4-21) in the isolated hepatic perfusion group. In the control group, 48% of patients received chemotherapy, 39% received ICIs, and 11% received localized treatment interventions.

The estimated 6-month hepatic PFS rates were 63% and 13% in the isolated hepatic perfusion and control groups, respectively. The median hepatic PFS was 9.1 months (95% CI, 5.6-13.4) vs 3.3 months (95% CI, 2.9-4.0) in each respective group (HR, 0.21; 95% CI, 0.12-0.36; P <.0001). In the control group, the median hepatic PFS was 3.0 months (95% CI, 2.8-4.3) for patients receiving chemotherapy and 3.3 months (95% Ci, 2.8-5.1) among those receiving ICIs.

The median DOR was 13.7 months (95% CI, 11.6-18.3) vs 8.8 months (95% CI, 6.0-not evaluable) in the isolated hepatic perfusion and control groups, respectively. In patients who had a complete response, partial response, or stable disease and later progressed on treatment with isolated hepatic perfusion, the progressive sites were most commonly hepatic (52%), extrahepatic (26%), and simultaneous hepatic and extrahepatic progression (22%). In patients who were primarily resistant to isolated hepatic perfusion, 92% had primary progression in the liver, and 8% had extrahepatic progression.

SAEs occurred in 19.5% of patients receiving isolated hepatic perfusion and 6.5% of those receiving control treatment. In the isolated hepatic perfusion group, there was 1 instance each of SAEs including abdominal pain, liver artery thrombosis, hepatic infection, and sepsis. In the control group, there was 1 instance each of SAEs including atrial fibrillation, hypophysitis, colitis, and diarrhea.

Investigators reported 1 treatment-related death in the isolated hepatic perfusion group in which the patient underwent a liver artery dissection and died 16 days after treatment due to multiorgan failure secondary to liver artery thrombosis causing liver necrosis and aspiration pneumonia. All SAEs in the isolated hepatic perfusion group occurred within 3 months of treatment.

Reference

Bagge RO, 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