Researchers from the Moffitt Cancer Center have demonstrated significant improvements in treating metastatic uveal melanoma using a novel liver-directed therapy. The phase 3 FOCUS trial showed that the melphalan hepatic delivery system more than doubled progression-free survival compared to standard treatments for this rare and aggressive eye cancer.
Uveal melanoma, which originates in the eye and frequently metastasizes to the liver, has historically been resistant to conventional therapies. The new approach delivers the chemotherapy drug melphalan directly to the liver through a specialized percutaneous delivery system.
"This is the second publication in Annals of Surgical Oncology on the results of the FOCUS trial and definitely shows that treatment with the melphalan hepatic delivery system can help control the cancer in the liver," said Dr. Jonathan Zager, surgical oncologist in the Cutaneous Oncology Department at Moffitt and lead author of the study. "The treatment provides an option that does not interfere with their quality of life and gives patients a chance at longer survival."
Significant Clinical Improvements
The multi-institutional study compared outcomes between patients receiving the melphalan hepatic delivery system and those on standard care treatments. The results were striking:
- Median progression-free survival increased from 3.3 months with standard care to 9.1 months with the melphalan system
- Overall disease control rate improved from 46.9% to 80%
- Objective response rate nearly tripled from 9.4% to 27.5%
- Median overall survival extended from 14.5 months to 18.5 months
These improvements represent a substantial advance for patients with limited treatment options. The U.S. Food and Drug Administration granted approval for the melphalan hepatic delivery system in August 2023 based on these compelling results.
How the Treatment Works
The melphalan hepatic delivery system employs a targeted approach that minimizes systemic exposure to chemotherapy. During the procedure, doctors use specialized catheters and balloons inserted percutaneously to isolate the liver's blood supply. This isolation allows for the delivery of high-dose melphalan directly to the liver where the cancer has spread.
Critically, the system filters the drug before it can circulate throughout the body, significantly reducing the typical side effects associated with traditional chemotherapy. While some adverse events were observed—primarily related to blood cell count changes—these were generally manageable with standard outpatient care and often resolved with observation alone.
A Challenging Cancer
Metastatic uveal melanoma presents unique treatment challenges. As the most common primary eye cancer in adults, uveal melanoma has a high propensity to spread to the liver, at which point prognosis has traditionally been poor.
"This new treatment gives hope to patients with this historically tough-to-treat cancer," Dr. Zager noted. The targeted nature of the therapy addresses the primary site of metastasis while preserving quality of life—a crucial consideration for patients facing limited survival time.
Future Directions
While the current results are promising, researchers acknowledge the need for additional studies to fully understand the long-term benefits of the melphalan hepatic delivery system. Future research will explore potential combinations with other emerging therapies to potentially enhance outcomes further.
The FOCUS trial was sponsored by Delcath Systems, Inc., the developer of the melphalan hepatic delivery system. This collaboration between industry and clinical researchers exemplifies the type of partnership that can accelerate the development of novel treatments for rare cancers with significant unmet needs.
For patients with metastatic uveal melanoma, this advancement represents a meaningful step forward in a therapeutic landscape that has seen little progress until recently. The ability to effectively target liver metastases while minimizing systemic toxicity offers new hope for extending and improving the lives of those affected by this challenging disease.
