Melanoma is a deadly form of skin cancer and the sixth most common form of cancer in the US. Approximately 70,000 new cases of melanoma are diagnosed each year in the US; of those, 8,000 people will die of the disease. The most common sites of metastases (spread) are under the skin, lymph nodes, lungs, liver, brain, and bone. Researchers from UCLA’s Jonsson Comprehensive Cancer Center joined forces with scientists from 12 other sites in the US and Australia. The results of their research were published in the February 23, 2012 edition of The New England Journal of Medicine. The report notes that Zelboraf, a newly approved drug for patients with metastatic melanoma, nearly doubles their average survival times. The data was derived from an international Phase II study of the drug, which included 132 patients followed for at least one year.
According to the study authors, patients with metastatic melanoma typically survive about nine months. However, patients who received Zelboraf survived an average of 15.9 months, noted study senior author Dr. Antoni Ribas, a professor of hematology/oncology and a researcher at UCLA’s Jonsson Cancer Center. He noted, “This study shows that Zelboraf changes the natural history of this disease. 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.”
Zelboraf, which is a tablet taken twice daily, blocks a mutated BRAF protein; approximately 50% of patients with metastatic melanoma (4,000 individuals each year) have the BRAF mutation and can be treated with Zelboraf, noted Dr. Ribas. He added that of those, 53% have an objective response to the drug, which is defined as shrinkage by more than 30%. An additional 30% of patients experience a less significant response. Only 14% of patients with the BRAF mutation failed to respond to Zelboraf. In addition, he noted, the medication represents a breakthrough in treating metastatic melanoma. Prior to this, 10% or less of patients with this advanced form of the disease responded to any of the available conventional treatments. Dr. Ribas explained, “We knew this drug would make the melanomas shrink in a large proportion of patients and that it worked better than chemotherapy… We did not know that patients taking Zelboraf were living longer until now.”
The main limitation with the therapy is that the tumors eventually become resistant to Zelboraf; however, the UCLA researchers are studying this resistance and have discovered several mechanisms by which the cancer accomplishes this. Jonsson Cancer Center researchers are currently seeking agents to target that resistant. “While the problem of relapse and resistance is great, this study provides evidence that in some patients, their melanoma is controlled for over two years on the medication," noted study first author Dr. Jeffrey Sosman, director of the melanoma program at Vanderbilt-Ingram Cancer Center and co-principal investigator of the study.
In August 2011, Zelboraf was approved by the U.S. Food and Drug Administration (FDA) for use in metastatic melanoma. For Santa Ana, CA resident Louise Belley, 60, Zelboraf has allowed her to live much longer than her physicians initially predicted; last June she was able to see her daughter graduate from college. In November 2007, Ms. Belley was diagnosed with metastatic melanoma. 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.
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