CHICAGO — Percutaneous hepatic perfusion with melphalan improved local disease control, but not overall survival when compared with best available care in patients with ocular or cutaneous melanoma that had metastasized to the liver.
Chemoembolization is the standard of care in patients with hepatic metastases from ocular melanoma, a group that made up about 88% of the trial population. Systemic chemotherapy or immunotherapies do not appear to alter the natural history of the disease, which has a one-year survival of about 10%.
“Increased drug delivery achieved through novel regional therapeutic approaches may increase efficacy for a given agent (versus systemic administration) by overcoming a low therapeutic index,” said Dr. James Pingpank, Jr. who presented the late-breaking abstract at the annual meeting of the American Society of Clinical Oncology.
Forty-four patients were randomized to hepatic perfusion and 49 to best available care by the treating physician. More than half, 55%, of the control arm, crossed over to receive hepatic perfusion after hepatic progression.
High-dose melphalan at 3.0 mg/kg was infused into the hepatic artery via a percutaneously placed catheter with hepatic venous hemofiltration using a retrohepatic, double-balloon catheter and hemofiltration cartridges. Patients underwent 4 to 6 procedures at 28- to 35-day intervals.
The device and drug combination is under consideration by the Food and Drug Administration.
When compared with best available care, percutaneous hepatic perfusion increased median hepatic progression-free survival from 49 days to 245 days (hazard ratio 0.30, logrank P less than .0001), and overall progression-free survival from 46 days to 186 days (HR. 0.40, logrank P less than .0001).
No patients progressed while on hepatic perfusion with melphalan, and there were no differences in progression-free survival of ocular vs. cutaneous melanoma, said Dr. Pingpank of the University of Pittsburgh Hillman Cancer Center in Pittsburgh.
Median overall survival was similar at 301 days for best available care and 298 days for hepatic perfusion (HR 0.92, logrank P = .77). This was likely due to the high crossover rate, he said. When overall survival was examined in the control arm alone, it reached 398 days in patients who crossed over vs. 124 days for those who did not (logrank P = .0117).
Invited discussant Dr. Dirk Schadendorf, director of dermatology at University Hospital Essen in Essen, Germany, took issue with the high crossover rate and said a previous German trial (Br. J. Cancer 2002;87:840-5 also failed to show a significant survival advantage for intraarterial or IV fotemustine plus interferon-alpha and interleukin 2 in metastatic ocular melanoma.
“The clinical benefit besides local control is open and has not been answered by this trial,” he said. “The crossover in my view is a clear sign of bias and is not proving this treatment is of any benefit to the patient.”
Dr. Schadendorf said that additional relevant information is missing, such as the number of patients with liver-only metastases compared with other sites of metastasis, thus making it difficult to determine whether there is any potential patient imbalance between arms.
The most common therapy of the primary tumor was radiation in 52% of the experimental arm and 49% of the control arm, roughly 85% of patients had an ECOG performance status of 0, and their mean age was 55 years.
Expansion of the single-institution study to multiple centers proved safe and effective, Dr. Pingpank said. The most common grade 3/4 treatment-related toxicities in 40 evaluable patients receiving 116 perfusion treatments were thrombocytopenia (74%), neutropenia (61%), and anemia (47%). Three treatment-related deaths occurred, two due to neutropenic sepsis and one to hepatic failure.
Study sponsor Delcath Systems, Inc. provided melphalan and double-balloon catheters for the trial. The researchers disclosed serving on the scientific advisory board for and receiving research support from Delcath. Dr. Schadendorf disclosed honoraria or an advisory/consultancy role with AZD, Bristol-Myers Squibb, Plexxikon, Roche, Schering-Plough, and Bayer Schering Pharma.