Dr. Ribas on MAPK Inhibition With Dabrafenib and Trametinib

Antoni Ribas, MD, Department of Medicine, Division of Hematology-Oncology; Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (UCLA), describes the unique combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib, which both inhibit activating mutations in the mitogen-activated protein kinase (MAPK) pathway.

Both dabrafenib and trametinib are being investigated as single agents and in combination for patients with metastatic melanoma who harbor BRAF V600 gene mutations. Research into the two drugs as monotherapies and in combination was presented at the American Society of Clinical Oncology (ASCO) annual meeting in June and is published in The New England Journal of Medicine.

The unique combination of dabrafenib and trametinib prevents the development of MAPK-driven acquired resistance. Additionally, the combination is able to block the formation of the secondary cutaneous squamous cell carcinomas that are common with single agent BRAF inhibitors. The unique ability to increase antitumor activity while decreasing toxicities is an uncommon trait for a combination therapy, Ribas notes.

Further data on the combination of trametinib and dabrafenib was presented at the European Society for Medical Oncology (ESMO) congress held in Vienna, Austria, from September 28 - October 2, 2012. View updated data.