Approach Improves Outcomes in Melanoma With Liver Metastasis

No Overall Survival Benefit to Crossover Muddies Survival Analysis

Roxanne Nelson

September 24, 2011

September 24, 2011 (Stockholm, Sweden) — Percutaneous hepatic perfusion appears to extend progression-free survival in melanoma patients with liver metastases, according to data presented here at the 2011 European Multidisciplinary Cancer Congress.

Ocular or uveal melanoma frequently metastasizes to the liver; once this occurs, prognosis is usually poor. Between 50% and 60% of patients experience a recurrence, and median survival for those patients is 2 to 7 months. Approximately 10% of patients will be alive at 1 year.

However, patients who received percutaneous hepatic perfusion using melphalan had an overall progression-free survival of 6.1 months; in those who received best alternative care (control group), it was 1.6 months.

"Increased drug delivery achieved through novel regional approaches may increase the efficacy of a drug like melphalan, which has limited use with systemic administration in this type of malignancy," said lead author James Pingpank, MD, associate professor of surgery at the University of Pittsburgh Cancer Institute, Pennsylvania, who presented the data.

This is the first phase 3 study of percutaneous hepatic perfusion in patients with liver-dominant metastatic melanoma, and it showed that the overall response rates and progression-free survival were significantly improved, providing a new treatment option for the disease. Dr. Pingpank pointed out that results from the study were initially reported at the 2010 annual meeting of the American Society of Clinical Oncology, and that here he was reporting follow-up data.

No Overall Survival Benefit

There was no significant difference in overall survival, however, between the 2 treatment groups. Survival at 1 year was 29% in the percutaneous infusion group, and 26% in the control group.

Because the trial was not designed to show an overall survival benefit and most of the cohort lacked any other treatment option, crossover of those in the control group to the percutaneous infusion group was permitted. Approximately half (51%) of all patients in the control group crossed over.

"Because of the crossover, we did not see any difference in overall survival in this trial," Dr. Pingpank explained during a press briefing held ahead of the presentation.

Met Primary End Point

Percutaneous hepatic infusion is designed to saturate the liver with high doses of chemotherapy using a minimally invasive procedure.

In their study, Dr. Pingpank and colleagues randomized 93 patients with uveal melanoma from 10 clinics in the United States to either percutaneous hepatic infusion or best alternative care. Patients received melphalan 3 mg/kg of ideal body weight infused through the hepatic artery over 30 minutes.

The type of alternative treatment was determined by the patient's clinician, and consisted of interleukin 2, ipilimumab, transcatheter arterial chemoembolization, systemic chemotherapy, or inclusion in a clinical trial.

The primary end point of the study was hepatic progression-free survival. Secondary end points included overall response rate, progression-free survival, and overall survival.

Investigator-assessed hepatic progression-free survival was significantly better in the experimental group than in the control group (8.1 vs 1.6 months; hazard ratio, 0.34; P < .0001), with a 6.5-month difference at the median.

Overall survival was 11.4 months in the percutaneous infusion group, and 9.9 months in the control group. The authors note that the patients who crossed over appeared to do well, despite being among the sickest in the cohort, and survived for an average of 9.2 months without liver metastasis and 6.5 months without any overall progression of the disease.

Adverse effects were more severe in patients who received percutaneous hepatic perfusion than among those who received best alternative care. However, noted Dr. Pingpank, they generally resolved within a short period of time.

The majority of toxicities were based on systemic delivery, he explained. "The filtering system was quite efficient, but we did see some drugs get into the system," he said. "The majority of patients had treatable thrombocytopenia or neutropenia."

The device that delivers and filters the melphalan has already been approved in Europe for use in all malignant liver tumors. Approval is currently pending melanoma only in the United States.

"Patients with uveal melanoma and liver metastasis do extremely poorly, so this study is very important," said Jean-Charles Soria, MD, who comoderated the session.

"This is something that oncologists need to think about it," added Dr. Soria, who is a medical oncologist at Institut Gustave Roussy, Paris, France, and professor of medicine and medical oncology at Paris University XI. Dr. Soria pointed out that when he has a patient with lung cancer with massive liver involvement, he is using this approach.

"This is a novel regional strategy of high value, and a nice demonstration of a multidisciplinary approach," he added.

2011 European Multidisciplinary Cancer Congress (EMCC): Abstract 9304. Presented September 24, 2011.

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