Percutaneous hepatic perfusion using a melphalan hepatic delivery system (melphalan/HDS) may be an effective treatment option in patients with unresectable uveal melanoma that has metastasized to the liver, according to a recent study published by Zager et al in the Annals of Surgical Oncology.
Background
Metastatic uveal melanoma is challenging to treat and often has poor outcomes. Liver metastases leading to liver failure is common, and therapies targeted to the liver are currently employed in treatment, including transarterial chemoembolization (TACE), radioembolization or immunoembolization, thermal ablation, and loco-regional perfusion therapies such as melphalan/HDS.
The melphalan/HDS treatment was approved by the U.S. Food and Drug Administration in August 2023. This percutaneous hepatic perfusion approach is minimally invasive and delivers a high dose of melphalan directly to the liver. The drug is then filtered out to avoid systemic exposure to melphalan.
Study Details
In the phase III FOCUS trial, researchers sought to evaluate the efficacy and safety of percutaneous hepatic perfusion using melphalan/HDS compared to best alternative care (investigator’s choice of TACE, pembrolizumab, ipilimumab, or dacarbazine). Eligible patients (n = 85) were randomized 1:1 to receive melphalan/HDS or BAC (investigator’s choice of TACE, pembrolizumab, ipilimumab, or dacarbazine).
The study was initiated as a two-arm, open-label, controlled, randomized study, but was later amended to a single-arm study because enrollment was slow and many patients were reluctant to receive best alternative care. For this reason, all efficacy analyses that were performed on the randomized study were considered exploratory.
The researchers reported that patients who received the melphalan/HDS experienced more favorable outcomes compared with those who received best alternative care. The median progression-free survival among the patients in the melphalan/HDS group was 9.1 months vs 3.3 months in the best alternative care group. The objective response rate was 27.5% vs 9.4%, and median overall survival was 18.5 months vs 14.5 months. At 1-year of follow-up, overall survival was 79% in the melphalan/HDS arm vs 67% in the best alternative care arm.
Safety
Patients treated with melphalan/HDS experienced more adverse and serious adverse events than those who were treated with best alternative care. Hematologic adverse events in the melphalan/HDS group included severe thrombocytopenia, leukopenia, neutropenia, and anemia. Most of these were treated in the outpatient setting or with observation. Adverse events in the best alternative care group included alanine aminotransferase and aspartate aminotransferase elevation and hypertension, and nausea/vomiting, leukopenia, and abdominal pain. No hematologic serious adverse events were noted in the best alternative care group.
Two deaths were reported in the melphalan/HDS group due to acute hepatic failure (1) and bacterial peritonitis (1); neither of these deaths was thought to be related to study treatment.
Conclusions
The researchers indicated that the minimally invasive liver-targeted approach could reduce systemic adverse effects in this seriously ill population. Further studies are expected to examine the benefits of melphalan/HDS and to identify whether this could be combined with other new therapies.
“This new treatment gives hope to patients with this historically tough-to-treat cancer,” said lead study author Jonathan Zager, MD, a surgical oncologist in the Cutaneous Oncology Department at Moffitt Cancer Center. “This is the second publication … on the results of the FOCUS trial and … shows that treatment with the [melphalan/HDS] can help control the cancer in the liver," he concluded.
Disclosure: The research in this study was sponsored by Delcath Systems. For full disclosures of the study authors, visit link.springer.com.
