Metastatic uveal melanoma, the most common form of ocular melanoma, remains one of the most challenging cancers to treat once it spreads beyond the eye. Unlike cutaneous melanoma, uveal melanoma often responds poorly to traditional immunotherapies. When metastasis occurs, the liver becomes the dominant site of disease in nearly 90% of patients, making liver-directed treatments an important component of care.
A recent clinical study known as the CHOPIN trial explored whether combining regional liver therapy with immunotherapy could improve outcomes for patients with liver-dominant metastatic uveal melanoma.
Percutaneous hepatic perfusion (PHP) is a specialized procedure that delivers high-dose melphalan chemotherapy directly to the liver, allowing doctors to target metastatic tumors while limiting exposure to the rest of the body. While PHP has shown strong activity in controlling liver tumors, it does not address cancer that may spread outside the liver.
Researchers designed the CHOPIN trial to test whether adding **dual checkpoint immunotherapy—ipilimumab and nivolumab—**could enhance the effects of PHP and potentially stimulate a stronger systemic immune response.
The randomized phase 2 trial included 76 patients with unresectable liver-dominant metastatic uveal melanoma who had not previously received systemic therapy. Participants were assigned to receive either PHP alone or PHP combined with ipilimumab and nivolumab.
Results from the study were encouraging. Patients receiving the combined therapy experienced a significantly higher one-year progression-free survival rate of 54.7%, compared with 15.8% in the PHP-only group. Median progression-free survival also improved, increasing to 12.8 months with the combination therapy versus 8.3 months with PHP alone.
Tumor responses were also notably higher in the combination group. The objective response rate reached 76.3%, including five complete responses, compared with 39.5% in patients receiving PHP alone.
Although the study was not primarily designed to evaluate overall survival, results showed a promising trend. Median overall survival reached 23.1 months with the combination therapy compared to 19.6 months with PHP alone.
As expected with more aggressive treatment, toxicity rates were higher in the combination group, but most adverse events were considered manageable with proper monitoring and supportive care.
Overall, the CHOPIN trial provides important evidence that integrating liver-directed therapy with systemic immunotherapy may represent a new treatment strategy for metastatic ocular melanoma, offering renewed hope for patients facing this rare and aggressive disease.