Trametinib


Trametinib is a cancer drug. It is a MEK inhibitor drug with anti-cancer activity.
It inhibits MEK1 and MEK2.
Trametinib had good results for metastatic melanoma carrying the BRAF V600E mutation in a phase III clinical trial. In this mutation, the amino acid valine at position 600 within the BRAF protein has become replaced by glutamic acid making the mutant BRAF protein constitutively active.
In May 2013, trametinib was approved as a single-agent by the Food and Drug Administration for the treatment of patients with V600E mutated metastatic melanoma.
Clinical trial data demonstrated that resistance to single-agent trametinib often occurs within 6 to 7 months. To overcome this, trametinib was combined with the BRAF inhibitor dabrafenib. As a result of this research, on January 8, 2014, the FDA approved the combination of dabrafenib and trametinib for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma. On May 1, 2018, the FDA approved the combination dabrafenib/trametinib as an adjuvant treatment for BRAF V600E-mutated, stage III melanoma after surgical resection based on the results of the COMBI-AD phase 3 study, making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma.

Other uses

In a person with a sequence variant in the ARAF gene, trametinib helped the lymphatic system to remodel toward a healthier state, reducing lymphatic edema. This benefit would not occur in most people because it is specific to genomes similar to the reported one, but it is potentially lifesaving for the few people with such genomes. This case provides an example of what precision medicine can accomplish.