After UCLA-Led Study, Combo Drug Therapy Approved by FDA to Treat Advanced Melanoma

A researcher at the UCLA Jonsson Comprehensive Cancer Center helped develop a combination drug therapy that was approved today by the U.S. Food and Drug Administration to treat metastatic melanoma. The therapy shows great promise for extending the lives of people with an advanced form of the disease, and it does so without causing a secondary skin cancer, a side effect seen in some patients who took only one of the drugs.

The study was conducted at UCLA and 135 other sites in the United States, Europe, Australia and Russia.

"Today's approval is a significant advance in the treatment of metastatic melanoma," said Dr. Antoni Ribas, the study's senior investigator and a researcher at the UCLA Jonsson Comprehensive Cancer Center. "For patients with a BRAF mutated melanoma, the combination has higher activity to shrink their tumors, and with less side effects than the drugs on their own."

The drugs, vemurafenib (marketed under the brand name Zelboraf) and cobimetinib (Cotellic), were tested in combination on approximately 495 patients who had BRAF V600, a mutation-positive advanced melanoma. Because so many of the people in the early stages of the study showed significantly better responses than those who had been prescribed vemurafenib alone, the research was continued and the FDA granted the therapy "priority review" status, leading to its approval.

An estimated 70,000 new cases of melanoma are diagnosed in the United States annually, and 8,000 people will eventually die of the disease each year. About half the people with metastatic melanoma have a mutated protein called BRAF mutation.

This mutation can be treated with vemurafenib, which was recently approved by the FDA. Researchers previously discovered that the BRAF mutation gives melanoma the signal to grow continuously as a cancer and vemurafenib could block the signal, but with time the cancer found a way around it to regrow.

The study showed that when the experimental drug cobimetinib is added, the combination works better and for much longer, Ribas said.

In addition, combining cobimetinib with vemurafenib also decreased incidence of secondary skin cancer that occurs in 25 percent of patients given vemurafenib alone, the research found.

Dr. Kenneth Dorshkind, interim director of the Jonsson Comprehensive Cancer Center and a professor of pathology and laboratory medicine at the David Geffen School of Medicine at UCLA, said that though there have been significant advances in treatment for metastatic melanoma in recent years, there remains a high unmet need for effective new therapies.

"When melanoma is diagnosed early it is generally a curable disease, but most people with advanced melanoma have a poor prognosis," Dorshkind said. "Based on the pioneering work conducted at UCLA, we are making significant advances against this deadly disease and patients now have more treatment options."

The scientific basis of this research builds upon prior studies at UCLA led by Dr. Roger Lo, a Jonsson Comprehensive Cancer Center member and associate professor of medicine, who had described the mechanisms of how melanoma became resistant to vemurafenib and that the addition of a drug like cobimetinib would prevent these mechanisms.

Ribas, who also is a professor of medicine in the division of hematology-oncology at the David Geffen School of Medicine at UCLA, said further research into the therapy is ongoing, as are efforts to improve its effectiveness and increase the percentage of people who could benefit from the treatment.

About UCLA's Jonsson Comprehensive Cancer Center

UCLA's Jonsson Comprehensive Cancer Center has more than 450 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2015, the Jonsson Cancer Center was ranked the sixth cancer center nationwide by U.S. News & World Report.