On November 10, the Food and Drug Administration (FDA) approved a combo drug therapy to treat advanced melanoma. The approval followed the findings of an international UCLA-led study. The study found that a new therapy, which combines vemurafenib (Zelboraf), a drug used to treat melanoma, with cobimetinib (Cotellic) extends lives and decreases the risk of side-effects in men and women with melanoma. The study was conducted at UCLA and 135 other sites in the US, Europe, Australia, and Russia.
UCLA Jonsson Comprehensive Cancer Center researchers took part in the development of the new combo therapy. The study authors note that the treatment shows great promise for extending the lives of individuals 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. “Today’s approval is a significant advance in the treatment of metastatic melanoma,” noted senior author Antoni Ribas, MD, a researcher at the UCLA Jonsson Comprehensive Cancer Center. He added, “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 combination of Zelboraf and Cotellic, were tested on approximately 495 patients who had BRAF V600, which is a mutation-positive advanced melanoma. Because so many of the subjects in the early stages of the study showed significantly better responses than those who had been prescribed Zelboraf alone, the research was continued and the FDA granted the therapy “priority review” status, which resulted in its approval.
Each year in the United States, an estimated 70,000 new cases of melanoma are diagnosed, and 8,000 will eventually die of the disease each year. Approximately 50% of patients with metastatic melanoma have a mutated protein called BRAF mutation. This mutation can be treated with Zelboraf, which was recently approved by the FDA. The investigators previously discovered that the BRAF mutation gives melanoma the signal to grow continuously as a cancer and Zelboraf could block the signal, but with time the cancer found a way around it to regrow. Dr. Ribas explained that the study found that when the experimental drug Cotellic is added, the combination works better and for much longer. Furthermore, the study found that combining the two drugs also decreased incidence of secondary skin cancer that occurs in 25% of patients given Zelboraf alone.
Kenneth Dorshkind, PhD, 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, explained that, although there have been significant advances in treatment for metastatic melanoma in recent years, there remains a strong unmet need for effective new therapies. He said, “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 is based upon prior studies at UCLA led by Dr. Roger Lo, MD, PhD, 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 such as Cotellic would prevent these mechanisms. Dr. Ribas 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.