|Other names||GSK1120212, trametinib dimethyl sulfoxide (DMSO)|
|Drug class||MEK inhibitor|
|Main uses||Melanoma, non-small cell lung cancer, anaplastic thyroid cancer|
|Side effects||Rash, diarrhea, tiredness, swelling, nausea, fever|
|Typical dose||2mg OD|
|Chemical and physical data|
|Molar mass||615.404 g·mol−1|
|3D model (JSmol)|
Trametinib, sold under the trade name Mekinist, is a medication used to treat certain types of melanoma, non-small cell lung cancer, and anaplastic thyroid cancer. Specifically it is used for cancers with the BRAF V600E mutation. It is taken by mouth.
Common side effects include rash, diarrhea, tiredness, swelling, nausea, and fever. Other side effects may include new cancers, bleeding, colitis, blood clots, and heart failure. Use during pregnancy may harm the baby. It is a MEK inhibitor and blocks both MEK1 and MEK2.
Trametinib was approved for medical use in the United States in 2013 and Europe in 2014. In the United Kingdom a month of medication costs the NHS about £4,800 as of 2021. This amount in the United States costs about 13,200 USD.
It is used in melanoma with a specific mutation. In this mutation, the amino acid valine (V) at position 600 within the BRAF protein has become replaced by glutamic acid (E) making the mutant BRAF protein constitutively active.
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.
It is taken at a dose of 2mg per day.
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.
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