Better Together: Combining BRAF and MEK Inhibitors Prolonged Progression-Free Survival in Metastatic Melanoma

At their full monotherapy doses, the combination of dabrafenib and trametinib was effective and safe, despite some toxic effects.

Blocking MAPK signaling prolongs survival and progression-free survival in metastatic melanoma related to BRAF V600 mutations. BRAF inhibitors such as dabrafenib restrain cancer cell growth, and MEK inhibitors such as trametinib block the protein's resistance-promoting effects (see JW Dermatol Jun 6 2012). Nevertheless, after about 6 months of therapy with these inhibitors, half of patients develop resistance to BRAF inhibition. Investigators assessed the safety and duration of effect of various doses of dabrafenib and trametinib, as monotherapy and combined. The study was funded by the maker of both drugs.

In 162 patients randomized to receive dabrafenib monotherapy or one of two combination regimens (150 mg of dabrafenib plus 1 or 2 mg of …

Reviewing Author

Hensin Tsao, MD, PhD

Disclosures

Consultant / advisory board Lubax; WorldCare Clinical

EquityLubax

Grant / Research support NIH; Department of Defense; American Skin Association; Piramal

Editorial boardsBritish Journal of Dermatology; Journal of the American Academy of Dermatology; Journal of Investigative Dermatology

Leadership positions in professional societies American Academy of Dermatology (Chair, Skin Cancer and Melanoma Committee); American Board of Dermatology (Director)