Immune drugs hold hope of "clinical cure" for deadly skin cancer

A new generation of drugs designed to trigger the immune system to fight cancer is offering the prospect of a "clinical cure" for some melanoma skin cancer patients who until a few years ago were more likely to be facing a swift death.

Cancer specialists gathering for a European conference at the weekend said the so-called immunotherapy drugs, a class led by Bristol-Myers Squibb's Yervoy, or ipilimumab, have transformed an area of oncology in which until recently doctors barely had time to get to know their patients.

Stephen Hodi, assistant professor of medicine at the Dana-Farber Cancer Institute in the United States, said he was cautious about using the term cure, but described recent advances as a "paradigm shift".

At the least, he said, the success of this new generation of medicines means some melanoma patients would now be living with a chronic disease, rather than facing imminent death.

"This is a really amazing time ... A few years ago we could never have imagined using the C-word, cure, in melanoma," he said. "But we are headed that way."

"Ipilimumab opened a door, and now the field is moving extremely fast," he told Reuters at the European Cancer Congress (ECC) in Amsterdam.

Yervoy, approved by regulators in 2011, was hailed as a breakthrough treatment in melanoma after it became the first drug ever to extend survival in patients with advanced forms of the melanoma, the deadliest form of skin cancer.

A type of drug known as a human monoclonal antibody, it activates the body's immune system to fight the cancer by targeting a protein receptor called Cytotoxic T-Lymphocyte Antigen 4, or CTLA-4.

On average, Yervoy added only about four months of life in pivotal trials, but around 20 percent of patients had an impressively durable response to the drug.

Hodi presented new data at the ECC from the largest and longest study of overall survival for patients treated with Yervoy which showed some of them can survive for up to 10 years.

Alexander Eggermont of the Institut Gustave Roussy Comprehensive Cancer Center in France, who specializes in the treatment of melanoma, said Hodi's results suggested some patients could be effectively cured of their cancer - a concept known as a "clinical cure" - with the drug helping the immune to keep the disease in check.

"Patients apparently can keep residual tumors under control for a long time when the immune system is properly 'reset', and the concept of 'clinical cures' becomes a reality," he said in a statement to the conference.

And with a next generation of immunotherapy drugs - designed to disable proteins called PD1 and PDL1 that prevent the immune system from spotting and attacking cancer cells - already being tested alone and in combination with Yervoy, there is "tremendous promise" in the treatment of melanoma, said Hodi.

Bristol-Myers Squibb is conducting late stage trials of its next-generation drug, nivolumab, in advanced melanoma, while rival U.S. drugmaker Merck is developing a competitor, lambrolizumab, which in early-stage trials helped shrink tumors in 38 percent of advanced melanoma patients.

Swiss drugmaker Roche's also has a leading contender - MPDL3280A - in this class.

"These (Yervoy) survival results could even double or triple with anti-PD1/PDL1 monoclonal antibodies, and metastatic melanoma could become a curable disease for perhaps more than 50 percent of patients over the coming five to 10 years," Eggermont said.

Research Gets to Root of Redheads' Higher Melanoma Risk

It's well known that natural redheads are at higher odds for deadly melanoma skin cancer, and new research in mice may help explain why.

Researchers at Harvard Medical School say the genetic mutation responsible for red hair and light skin also appears to promote a well-known cancer-causing pathway.

A person's hair color and skin tone are influenced by a gene receptor called melanocortin-1 (MC1R), and a mutation in MC1R accounts for the 1 percent to 2 percent of people who are born redheads.

In experiments with mice and cell cultures, researchers found that the same MC1R mutation -- called MC1R-RHC -- triggers a specific biochemical signaling pathway when a redhead is exposed to ultraviolet radiation from the sun and other sources.

This pathway, called P13K/Akt, has been tied to breast, ovarian and lung tumors, according to the study, which was published online Aug. 22 in the journal Molecular Cell.

"[The findings] provide a possible molecular mechanism as to why red-haired individuals harboring [these] mutations are much more susceptible to UV-induced skin damage than individuals with darker skin, resulting in a 10- to 100-fold higher frequency of melanoma," study co-senior author Wenyi Wei, an investigator at Beth Israel Deaconess Medical Center and an associate professor of pathology at Harvard, said in a medical center news release.

The researchers also said their findings are a starting point for future studies. For example, people who carry the MC1R mutation might be identified as being at higher skin cancer risk, or drugs that target the P13K/Akt pathway might help treat certain melanomas.

Melanoma is among the rarest of skin cancers, but it also is the most deadly, accounting for 75 percent of skin cancer deaths, the researchers said.

Researchers note that research conducted in animals often does not have the same results in humans.