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The Cutting Edge

A One-Two Punch to Skin Cancer

Treating metastatic melanoma by combining immunotherapy with a drug that inhibits the cancer-spreading activity of a common gene mutation significantly increased survival times in an animal model.About 50 percent of patients with metastatic melanoma have the BRAF mutation and can be treated with vemurafenib.

In a study by researchers at UCLA's Jonsson Comprehensive Cancer Center, animals that received a combination of the recently approved BRAF inhibitor vemurafenib and an engineered T-cell immunotherapy had better tumor responses and lived more than twice as long as those getting the BRAF inhibitor or immunotherapy alone. The findings provide strong support for testing the combination therapy in human clinical trials.

About 50 percent of patients with metastatic melanoma have the BRAF mutation and can be treated with vemurafenib. More than 50 percent of them respond well to the drug, but the responses usually last only a few months. With immunotherapy, fewer patients respond, but the responses are more durable.

By pairing these therapies in a one-two punch, researchers hope to maintain the high response rates associated with vemurafenib and combine them with the longer disease-free progression times seen with immunotherapy, says Richard Koya, M.D., Ph.D., assistant professor of surgical oncology. "The idea was to target two different aspects of anti-cancer biology, hitting the tumor cells themselves with the BRAF inhibitor and adding in T-cells educated to induce a specific anti-tumor immune response. The results we saw in this study were very promising."

The study was published in the journal Cancer Research.

The researchers also found that the BRAF inhibitor helped boost the power of the immunotherapy, creating a greater combination effect, says co-author Antoni Ribas, M.D., Ph.D., professor of hematology/oncology. "We found that both treatments were more effective when administered together, and we were surprised to see that a drug that should only be targeting the BRAF-mutant cancer cells was also having a beneficial effect on the T-cells." It is vital to develop new drugs to treat metastatic melanoma, as few options are available for patients, the researchers said. Vemurafenib works well, but most patients eventually relapse.

"This is a patient population that we are not able to cure," Dr. Koya said. "With what we have now, we are just prolonging their lives. We need to have more options, and we hope this combination therapy proves to be an effective alternative."


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