New melanoma drugs - why do so few benefit?

By Julie Steenhuysen

CHICAGO (Reuters) - When they work, new melanoma treatments that enlist the help of the immune system to attack tumors can have a stunning effect, in some cases arresting the deadly skin cancer for four years.

But typically just a handful of patients get that kind of response.

"We are in a situation where in some patients we see really dramatic and long-lasting effects. Some of the responses are phenomenal. Still, many patients don't respond," said Dr. Lynn Schuchter, a melanoma expert at the University of Pennsylvania.

"What we really are trying to understand is which patients should be treated with these drugs," she said in an interview.

Two big drugmakers -- Pfizer Inc and Bristol-Myers Squibb Co -- are the farthest along in developing these drugs, but both programs have had major setbacks in the past two months.

Pfizer in April said its targeted treatment tremelimumab did not work any better than chemotherapy in a large study.

And Bristol-Myers and its partner Medarex Inc in April said they would delay seeking marketing approval of ipilimumab for advanced melanoma after U.S. regulators asked for more proof that the drug, also a targeted treatment, helps people live longer.

Pfizer and Bristol-Myers released details from studies of these drugs at a meeting of the American Society of Clinical Oncology in Chicago this week.

"There is a small subset of patients that does very well, with major complete responses or durable partial responses," said Thomas Gajewski of the University of Chicago.

He said the problem is that on average, only about 10 percent of patients do this well, which is likely not enough to win marketing approval for the drugs.

"One of the main issues on a scientific level is to figure out who that 10 percent are," he said in an interview.

Melanoma accounts for about 3 percent of skin cancer cases but causes most skin cancer deaths, and doctors have few effective treatments to offer once the disease has spread.

In 2008 it will be diagnosed in 62,480 Americans and will kill 8,420, according to the American Cancer Society.

IMMUNE 'BRAKE'

Ipilimumab and tremelimumab are monoclonal antibodies -- targeted immune system proteins that interfere with another immune compound called CTLA-4.