Pegylated, standard interferon retain relevance in some melanoma cases

June 1, 2012

Interferon and the recently Food and Drug Administration-approved pegylated interferon remain relevant adjuvant therapies for patients with lymph node-positive melanoma, even in light of advances with CTLA4 blockade and BRAF-targeted therapies for late-stage disease, says Vernon K. Sondak, M.D., chairman, department of cutaneous oncology, Moffitt Cancer Center, Tampa, Fla.

Key Points

Tampa, Fla. - Interferon and the recently Food and Drug Administration-approved pegylated interferon remain relevant adjuvant therapies for patients with lymph node-positive melanoma, even in light of advances with CTLA4 blockade and BRAF-targeted therapies for late-stage disease, says Vernon K. Sondak, M.D., chairman, department of cutaneous oncology, Moffitt Cancer Center, Tampa, Fla.

For many years, dacarbazine (DTIC, Bayer) has been a chemotherapy staple used to treat stage 4 melanoma patients. Continued research has led to the development of two new therapies indicated for stage 4 unresectable metastatic melanoma; namely, ipilimumab (Yervoy, Bristol-Myers Squibb)and vemurafenib (Zelboraf, Genentech).

"These new drugs have been shown in randomized controlled phase 3 trials to improve the survival of patients with unresectable metastatic disease, which is beyond anything that would be treated in the adjuvant setting," Dr. Sondak says.

Even though ipilimumab and vemurafenib used for stage 4 disease improve overall survival compared to chemotherapy, Dr. Sondak says, there is still reason to use adjuvant therapy for stage 3 melanoma if it can improve overall survival.

According to Dr. Sondak, there is a small but real survival benefit for interferon, based on the meta-analysis data involving more than 8,000 patients on randomized trials. The magnitude of this survival benefit and even whether it exists at all has been debated, however.

"The meta-analysis data indicate that there is an estimated 10 percent relative improvement in overall survival with standard interferon. For a sentinel node-positive patient with a 70 percent five-year survival rate after surgery alone, 100 patients would have to be treated with the drug to 'cure' three patients, illustrating why the survival benefit is so controversial," Dr. Sondak says.

There is even less data to support whether pegylated interferon has any overall survival benefit, but if it does, it is also likely to be small or perhaps only confined to a subset of patients, he says.

Delineating differences

Although standard and pegylated interferon are related pharmacologically, they are designed to achieve the same end in a slightly different way. They are given in a very different schedule and duration of treatment as well.

Dr. Sondak says both of the interferons can potentially help prolong patients' lives in terms of extending relapse-free survival while newer and evolving therapies become more effective for stage 4 disease.

"Changes are coming rapidly enough that even a year or two delay in recurrence could result in a given patient having a better chance of success than they would have had otherwise. This is why the relapse-free survival benefit of interferons is as relevant today as it has ever been," he says.

Both ipilimumab and vemurafenib could be used in the adjuvant setting, Dr. Sondak says, and trials testing these drugs, including some trials comparing them to interferon, are under way.

Though clinical trial participation is encouraged, Dr. Sondak says the use of any of these new drugs as adjuvant therapy for stage 3 melanoma outside a trial is premature. He believes interferon remains a good treatment option for those who want to improve their long-term chances by delaying recurrence and hoping for even better treatments if and when they do eventually relapse.

Whether it is regular interferon at a very high dose or intermediate sustained doses, or pegylated interferon, Dr. Sondak says, it is not clear that the percent of people who are cured would be higher with a different dose or a different type of interferon.

"There are patients for whom pegylated interferon may represent a preferred option, and thoughtful discussions between patients and doctors represent the best way to select the treatment option most appropriate for a given individual - which sometimes is no treatment at all but other times will be one or the other type of interferon," Dr. Sondak says.

Disclosures: Dr. Sondak is a paid consultant for Merck.