Researchers from UCLA's Jonsson Comprehensive Cancer Center, together with scientists from 12 other sites in the United States and Australia, report for the first time that a newly approved drug for patients with metastatic melanoma nearly doubles median survival times, a finding that will change the way this deadly form of skin cancer is treated.

The data comes from an international Phase II study of Zelboraf that included 132 patients followed for at least one year.

Patients with this advanced form of melanoma that has spread to other organs typically survive about nine months. Patients taking Zelboraf, which blocks a mutated BRAF protein, survived an average of 15.9 months, said study senior author Dr. Antoni Ribas, a professor of hematology/oncology and a researcher at UCLA's Jonsson Cancer Center.

"This study shows that Zelboraf changes the natural history of this disease," Ribas said. "This data is beyond what I would have expected. We're seeing a significant number of patients with durable responses to the drug, and that the whole group of treated patients is living longer. These results tell us that this drug is having a very big impact, and this changes the way we treat metastatic melanoma."

The study in the peer-reviewed New England Journal of Medicine.

About 50 percent of patients with metastatic melanoma, or 4,000 people a year, have the BRAF mutation and can be treated with Zelboraf, a pill taken twice a day, Ribas said. Of those, 53 percent have an objective response to the drug, meaning their tumours shrink by more than 30 percent. An additional 30 percent of patients have tumour responses of lesser magnitude. Only 14 percent of patients with the BRAF mutation failed to respond to Zelboraf.

The drug represents a breakthrough in treating metastatic melanoma. Prior to this, 10 percent or less of patients with this advanced form of the disease responded to any of the available conventional treatments, Ribas said.

"We knew this drug would make the melanomas shrink in a large proportion of patients and that it worked better than chemotherapy," Ribas said. "We did not know that patients taking Zelboraf were living longer until now."

The main limitation with Zelboraf is that tumours eventually become resistant. But Jonsson Cancer Center researchers are studying this resistance and have uncovered several mechanisms by which the cancer gets around Zelboraf. Cancer center scientists currently are seeking agents to target those mechanisms, Ribas said.

For Louise Belley, 60, of Santa Ana, Zelboraf has allowed her to live much longer than her doctors initially predicted, and last June she was able to see her daughter graduate from college. Belley was diagnosed with metastatic melanoma in November of 2007. In June 2009, she was among the first people to get the drug when it was in Phase I studies at the Jonsson Cancer Center.

Her first CT scan in September 2009 after joining the trial - nearly two and a half years ago - was clear of any cancer, she said. Her scans remain clean today.

"At first I was devastated by my diagnosis, because I realised I was in a really bad place," Belley said. "But now I feel strongly that the chances are good that I will continue to be cancer free, and I plan to live every day to the fullest."

Zelboraf was approved by the U.S. Food and Drug Administration for use in metastatic melanoma in August of 2011. About 70,000 new cases of melanoma are diagnosed each year in the United States. Of those, 8,000 people will die of the disease.

"This trial shows a high rate of response to (Zelboraf) in patients with metastatic melanoma and activating BRAF mutations," the study states. "These results independently confirm the high response rate and response duration shown in a Phase I trial."

Source: University of California - Los Angeles Health Sciences