Triple Combo: Two Targeted Drugs Plus Immunotherapy Show Promise in BRAF-Mutant Melanoma

“Results of a new study by UCLA researchers has found that a groundbreaking new triple combination therapy shows promising signs of more effectively controlling advanced melanoma than previous BRAF + MEK inhibitor or BRAF inhibitor + immunotherapy combos alone, and with increased immune response and fewer side effects.

“An estimated 70,000 new cases of metastatic melanoma are diagnosed each year in the United States, and of those 8,000 will die of the disease. About 50 percent of these men and women (or 35,000 a year) have a mutated protein called a BRAF mutation, which in most cases allows melanoma to eventually build up a resistance to many drug therapies.

“In the new study led by UCLA Jonsson Comprehensive Cancer Center member Dr. Antoni Ribas and colleague Dr. Siwen Hu-Lieskovan, UCLA scientists combined targeted therapies utilizing a BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) with immunotherapy. The three together are shown to be more effective treatments by sensitizing the patients’ own immune system to enhance immunotherapy, and reduce the probability of the melanoma eventually developing resistance.

“This is a significant advance compared to previous drug combination findings, in which a combined BRAF inhibitor (vemurafenib) with immunotherapy (ipilimumab) caused serious liver toxicity in some patients, and the targeted therapies (BRAF and/or MEK inhibitors) became less effective and reactivated cancer cell growth.”

New Phase III study will test BRAF/MEK combination therapy in melanoma patients with BRAF positive mutation after following surgery

The London-based company, GSK has stared a phase III trial called “COMBI-AD” that will test the combination of a BRAF and MEK inhibitor, dabrafenib and trametinib in patients with BRAF V600E mutation-positive melanoma who have had surgery to remove their tumors (adjuvant setting). The placebo-controlled trial is testing how long the combo treatment can delay or prevent cancer recurrence in these high-risk patients. Two phase III combination trials are currently ongoing to test the combination versus monotherapy in metastatic BRAF-positive melanoma patients.