Trametinib

Trametinib (trade name Mekinist) is a cancer drug. It is a MEK inhibitor drug with anti-cancer activity.[1]

Trametinib
Clinical data
Trade namesMekinist
Other namesGSK1120212
License data
Pregnancy
category
  • US: D (Evidence of risk)
    ATC code
    Legal status
    Legal status
    Identifiers
    CAS Number
    PubChem CID
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    ECHA InfoCard100.158.135
    Chemical and physical data
    FormulaC26H23FIN5O4
    Molar mass615.39 g/mol g·mol−1
    3D model (JSmol)

    It inhibits MEK1 and MEK2.[1]

    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 (V) at position 600 within the BRAF protein has become replaced by glutamic acid (E) making the mutant BRAF protein constitutively active.[2]

    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.[3] Clinical trial data demonstrated that resistance to single-agent trametinib often occurs within 6 to 7 months.[4] To overcome this, trametinib was combined with the BRAF inhibitor dabrafenib.[4] 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.[5] 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,[6] making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma.[7]

    References
    1. Trametinib, NCI Drug Dictionary
    2. METRIC phase III study: Efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy (C) in patients (pts) with BRAFV600E/K mutant advanced or metastatic melanoma (MM).
    3. "GSK melanoma drugs add to tally of U.S. drug approvals". Reuters. May 30, 2013.
    4. Flaherty, Keith T.; Infante, Jeffery R.; Daud, Adil; Gonzalez, Rene; Kefford, Richard F.; Sosman, Jeffrey; Hamid, Omid; Schuchter, Lynn; Cebon, Jonathan; Ibrahim, Nageatte; Kudchadkar, Ragini; Burris, Howard A.; Falchook, Gerald; Algazi, Alain; Lewis, Karl; Long, Georgina V.; Puzanov, Igor; Lebowitz, Peter; Singh, Ajay; Little, Shonda; Sun, Peng; Allred, Alicia; Ouellet, Daniele; Kim, Kevin B.; Patel, Kiran; Weber, Jeffrey (November 1, 2012). "Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations". New England Journal of Medicine. 367 (18): 1694–703. doi:10.1056/NEJMoa1210093. PMC 3549295. PMID 23020132.
    5. "Dabrafenib/Trametinib Combination Approved for Advanced Melanoma". OncLive. January 9, 2014.
    6. Long, Georgina V.; Hauschild, Axel; Santinami, Mario; Atkinson, Victoria; Mandalà, Mario; Chiarion-Sileni, Vanna; Larkin, James; Nyakas, Marta; Dutriaux, Caroline; Haydon, Andrew; Robert, Caroline; Mortier, Laurent; Schachter, Jacob; Schadendorf, Dirk; Lesimple, Thierry; Plummer, Ruth; Ji, Ran; Zhang, Pingkuan; Mookerjee, Bijoyesh; Legos, Jeff; Kefford, Richard; Dummer, Reinhard; Kirkwood, John M. (9 November 2017). "Adjuvant Dabrafenib plus Trametinib in Stage III-Mutated Melanoma" (PDF). New England Journal of Medicine. 377 (19): 1813–1823. doi:10.1056/NEJMoa1708539. PMID 28891408.
    7. "FDA Approves Adjuvant Combo for BRAF+ Melanoma". www.medscape.com. WebMD LLC. Retrieved 2 May 2018.
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