Groundbreaking Immunotherapy Shows Promise in Melanoma Treatment

Treatment increases immune response with fewer side effects.

A groundbreaking therapy for advanced melanoma may offer a new treatment option that provides an increased immune response with fewer side effects for patients.

In a study published online March 18, 2015 in the journal Science Translational Medicine, the triple combination therapy for advanced melanoma showed promise in more effectively controlling the disease than BRAF + MEK inhibitor or BRAF inhibitor + immunotherapy combinations alone.

Approximately 35,000 patients newly diagnosed with melanoma each year have the BRAF protein mutation, which allows melanoma to develop resistance to numerous drug therapies. For the study, researchers from UCLA combined targeted therapies with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib with immunotherapy.

The triple combination was found to be more effective by sensitizing the immune system to improve immunotherapy, while reducing the probability of melanoma eventually developing resistance.

"The 2 drug combination of BRAF and MEK inhibitors works synergistically and decreases the side effects of the BRAF inhibitor or normal cells. We reasoned that this combo would allow us to synergize with immunotherapy without increasing toxicities," co-study lead Antoni Ribas, MD, said in a press release. "We have made incredible progress in the last three years of treating advanced melanoma, with six new drug therapies approved by the FDA. Half are immunotherapies and the other half are BRAF or MEK inhibitors. The next step is to figure out how to rationally combine them and merge their benefits in the clinic."

The new treatment represents a significant advance over prior drug combinations, the study noted. Treatments that combined the BRAF inhibitor vemurafenib with ipilimumab lead to serious liver toxicity in some patients, while targeted therapies with BRAF and/or MEK inhibitors over time lost efficacy and reactivated cancer cell growth.

The researchers have opened 2 clinical trials to evaluate the effectiveness of the triple combination therapy in advanced melanoma patients, with the initial findings scheduled to be presented at the annual American Society of Clinical Oncology meeting in May 2015.

"The triple combination of targeted therapies BRAF (dabrafinib) and MEK (trametinib) inhibitors with immunotherapy (tumor antigen-specific adoptive cell transfer or anti-PD1 antibody) makes immune therapy more effective at killing cancerous tumors and causes less toxicity,” co-study lead Siwen Hu-Lieskovan, MD, said in a press release. "We're trying to take advantage of the high response rate of the targeted therapy and durability of the immune therapy to induce a response that lasts in the majority of patients."