A UCLA-led research team has pinpointed a three-drug combination that could prove to be an effective new therapy for people with a specific type of advanced melanoma.
The approach shows promise for extending the lives of people with a type of melanoma that contains a potent gene mutation, BRAF V600E. In clinical trials, it appeared not to cause the debilitating side effects that are caused by a combination of one targeted drug and an immunotherapy drug.
The researchers found that people with the melanoma survived longer without the cancer progressing or growing when they received a combination of two targeted inhibitors that block the BRAF mutation (dabrafenib and trametinib) and an immune checkpoint inhibitor drug (pembrolizumab) as the initial treatment for their disease.
“Utilizing the three drugs together sensitized the patient’s own immune system to bolster the power of immunotherapy and block the growth of two genes—BRAF and MEK—that cause cancer cells to reproduce and grow out of control,” said Dr. Antoni Ribas, the paper’s senior author, a professor of medicine at the David Geffen School of Medicine at UCLA and director of the UCLA Jonsson Comprehensive Cancer Center’s Tumor Immunology Program.
The results of phase one and phase two clinical trials were published today in two papers in the journal Nature Medicine.
In the phase two trial, those who received the three-drug combination had progression-free survival—meaning that the disease did not worsen or progress—for an average of 16 months. Those who received trametinib, dabrafenib and a placebo lived for an average of 10.3 months without the disease progressing.
Approximately 94,000 Americans are diagnosed with melanoma annually, and around 7,000 people die of the disease each year. About half of the people who are diagnosed with metastatic melanoma carry the BRAF mutation.
Previous studies have found that using one of the three drugs alone can dramatically shrink tumors in a small percentage of people with melanoma. A majority of people on the treatment, however, do not see any benefit or end up experiencing a relapse. Two-drug combinations also have been tested, but they, too, have had limited success.