Trametinib, sold under the brand name Mekinist among others, is an anticancer medication used for the treatment of

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

and

glioma A glioma is a type of primary tumor that starts in the glial cells of the brain or spinal cord. They are malignant but some are extremely slow to develop. Gliomas comprise about 30% of all brain and central nervous system tumors and 80% of ...

. It is a

MEK inhibitor A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase enzymes MEK1 and/or MEK2. They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers. (See MAPK/ERK pathway#Clinical signifi ...

drug with anti-cancer activity. It inhibits MEK1 and MEK2. It is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

. The most common side effects include rash, diarrhea, tiredness, peripheral edema (swelling, especially of ankles and feet), nausea and acneiform dermatitis (acne-like inflammation of the skin). When taken in combination with dabrafenib the most common side effects include fever, tiredness, nausea, chills, headache, diarrhea, vomiting, joint pain and rash. In May 2013, trametinib was approved as a single-agent by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

for the treatment of people with V600E mutated metastatic melanoma. It was approved for medical use in the European Union in June 2014.

Medical uses

Trametinib, as monotherapy or in combination with

dabrafenib Dabrafenib, sold under the brand name Tafinlar among others, is an anti-cancer medication used for the treatment of cancers associated with a mutated version of the gene BRAF (gene), BRAF. Dabrafenib acts as an enzyme inhibitor, inhibitor of th ...

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of melanoma and glioma.

History

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

. As a result of this research, on 8 January 2014, the FDA approved the combination of dabrafenib and trametinib for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma. On 1 May 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.

Society and culture

Legal status

In November 2023, the Committee for Medicinal Products for Human Use (CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Spexotras, intended for the treatment of low- and high-grade glioma (LGG and HGG). The applicant for this medicinal product is Novartis Europharm Limited. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Spexotras was approved for medical use in the European Union in January 2024.

Research

Trametinib had good results for metastatic

carrying the BRAF

V600E V600E is a mutation of the '' BRAF'' gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600. It is a driver mutation in a proportion of certain diagnoses, including melanoma, hairy cell leukemia, papillary thyroid carcinoma ...

mutation in a phase III clinical trial. In this mutation, the amino acid

valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deproton ...

(V) at position 600 within the BRAF protein has become replaced by

glutamic acid Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α- amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can ...

(E) making the mutant BRAF protein constitutively active. Trametinib has been used off label to treat various RASopathies, including Noonan Syndrome and Primary Intestinal Lymphangiectasia.

References

{{Authority control Cancer treatments Cyclopropyl compounds Fluorobenzene derivatives Iodobenzene derivatives Acetanilides MEK inhibitors Drugs developed by GSK plc Drugs developed by Novartis Orphan drugs