Isolated Hepatic Perfusion May Improve Response and Survival Among Patients With Metastatic Uveal Melanoma

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An advanced surgical therapy may be more efficacious than conventional treatments for patients with uveal melanoma that has spread to the liver, according to results from the phase III SCANDIUM trial published by Bagge et al in the Journal of Clinical Oncology. Infusing the liver with high doses of the chemotherapy melphalan resulted in superior overall response, hepatic progression-free survival, and progression-free survival compared with best alternative care in previously untreated patients with isolated liver metastases.

In half of diagnosed patients, uveal melanoma causes liver metastases, which entail a highly unfavorable prognosis. After metastases in the liver have been found, a large majority of patients die within 1 year. Unfortunately, current treatments with immunotherapy or chemotherapy have only very limited effects.

Study Details and Results

In the Swedish SCANDIUM study, 87 previously untreated patients with isolated liver metastases from uveal melanoma were assigned to receive either investigator’s choice or the experimental therapy, known as isolated hepatic perfusion (IHP).

In the group undergoing IHP treatment, imaging showed that the tumors had shrunk in 39.5% of patients, compared to only 4.5% of the patients in the group receiving conventional treatment.

The median progression-free survival was 7.4 months in the IHP group vs 3.3 months in the control group (P < .0001), with a hazard ratio of 0.21 (95% confidence interval = 0.12–0.36), and the median hepatic progression-free survival was 9.1 months vs 3.3 months (P < .0001).

“This is the first therapy that’s been shown to shrink tumors as effectively for this group of patients. Our long-term goal is to enable the patients to become cancer-free, but to date we haven’t been able to say that the treatment can cure the patients,” said first author Roger Olofsson Bagge, MD, PhD, of the University of Gothenburg and senior consultant surgeon at Sahlgrenska University Hospital.

The IHP procedure is a large-scale surgical intervention involving open surgery in which the liver is surgically isolated and connected to a heart-lung machine. Extremely high doses of a chemotherapeutic agent are pumped through the lever for 1 hour, after which all the chemotherapy is flushed, and the liver is reconnected to the patient’s own circulation. Using this method, it is possible to administer an extremely high dose of chemotherapy concentrated to the part of the body that harbors the cancer cells, while the rest of the body do not get any negative effect.

“It’s a major operation involving open surgery, but next year we’ll be starting to use a minimally invasive method where the liver is isolated with balloons inserted into the blood vessels of the groin,” Dr. Olofsson Bagge said.

The study authors concluded their report by writing, “In summary, the present randomized controlled trial shows that a one-time treatment with IHP results in significantly superior antitumor responses and progression-free survival compared with treatment with chemotherapy or immune checkpoint inhibitors in treatment-naive patients with isolated liver metastases of uveal melanoma. The first analysis of overall survival, the primary endpoint of the study, is planned for 2023.”

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