Melanoma; Research team has pinpointed a three drug combination that could prove to be an effective new therapy for people with a specific type of advance 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; so it appear not to cause the debilitating side effects that are cause by a combination of one target drug and an immuno therapy drug.
The researchers found that people with the melanoma survive longer; so without the cancer progressing or growing when they receive a combination of two target inhibitors that block the BRAF mutation (dabrafenib and trametinib) and an immune checkpoint inhibitor drug (pembrolizumab) as the initial treatment for their disease.
The metastatic melanoma
Utilizing the three drugs together sensitize 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; so 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 publish today; so in two papers in the journal Nature Medicine. In the phase two trial, those who receive 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 receive trametinib, dabrafenib and a placebo live for an average of 10.3 months without the disease progressing.
Approximately 94,000 Americans are diagnose with melanoma annually; also around 7,000 people die of the disease each year. About half of the people who are diagnose with metastatic melanoma; so to carry the BRAF mutation. Previous studies have find that using one of the three drugs alone; so can dramatically shrink tumors in a small percentage of people with melanoma.
Earlier attempts to combine a target agent with an immune checkpoint inhibitor; so as a double combination therapy had debilitating side effects for patients, and it was just too toxic to continue testing; so they went back to the drawing board,” said Ribas, who is also the director of the Parker Institute for Cancer Immuno therapy Center at UCLA.
Double therapy combinations
One of the participants in that trial was Joanna, a former Wall Street trader and veteran hiker and snowboarder. In 2014, Joanna had golf ball size tumors throughout her body; she was diagnose with BRAF mutate advance melanoma. By the time the clinical trial began, she need a wheelchair to get around; so a far cry from the active life she was accustomed to.
Even though the trial was randomize, the three drug group had more patients; so with a poorer prognosis than the placebo arm. Regardless, people in the three drug group fared better; so with their progression free survival lasting an average of nearly six months longer than the average for those in the placebo arm.
The results of the triple therapy is so much more encouraging; so than double therapy combinations with these drug agents, Ribas said. With this triple combination, they’re doing two things at once; using the two inhibitors to block the cancer from spreading, and stimulating the immune system. An immune response has the ability to remember foreign invaders; also help protect the body from similar infections in the future; so enlisting an immune response to the cancer is aim at having more durable responses to the therapy.