Open main menu

Dabrafenib (trade name Tafinlar, GSK2118436) is a drug for the treatment of cancers associated with a mutated version of the gene BRAF. Dabrafenib acts as an inhibitor of the associated enzyme B-Raf, which plays a role in the regulation of cell growth. Dabrafenib has clinical activity with a manageable safety profile in clinical trials of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma.[1][2]

Dabrafenib
Dabrafenib.svg
Clinical data
Trade namesTafinlar
License data
Pregnancy
category
  • US: D (Evidence of risk)
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.215.965 Edit this at Wikidata
Chemical and physical data
FormulaC23H20F3N5O2S2
Molar mass519.56 g/mol g·mol−1
3D model (JSmol)

Approvals and indicationsEdit

The Food and Drug Administration initially approved dabrafenib as a single agent treatment for patients with BRAF V600E mutation-positive advanced melanoma on May 30, 2013.[3]

Clinical trial data demonstrated that resistance to dabrafenib and other BRAF inhibitors occurs within 6 to 7 months.[4] To overcome this resistance, the BRAF inhibitor dabrafenib was combined with the MEK inhibitor trametinib.[4] On January 8, 2014, the FDA approved this combination of dabrafenib and trametinib for BRAF V600E/K-mutant metastatic melanoma.[5][6] 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,[7] making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma.[8]

[April 2017] The European Union approved the combination with trametinib for BRAF V600-positive advanced or metastatic non small-cell lung cancer (NSCLC).[9]

Further readingEdit

U.S. National Center for Biotechnology Information: Medical Genetics Summaries - Dabrafenib Therapy and BRAF and G6PD Genotype

ReferencesEdit

  1. ^ Gibney, G. T.; Zager, J. S. (2013). "Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies". Expert Opinion on Drug Metabolism & Toxicology. 9 (7): 1. doi:10.1517/17425255.2013.794220. PMID 23621583.
  2. ^ Huang, T.; Karsy, M.; Zhuge, J.; Zhong, M.; Liu, D. (2013). "B-Raf and the inhibitors: From bench to bedside". Journal of Hematology & Oncology. 6: 30. doi:10.1186/1756-8722-6-30. PMC 3646677. PMID 23617957.
  3. ^ "GSK melanoma drugs add to tally of U.S. drug approvals". Reuters. May 30, 2013.
  4. ^ a b "Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations". 367 (18). New England Journal of Medicine. November 1, 2012: 1694–703. doi:10.1056/NEJMoa1210093. PMC 3549295. PMID 23020132.
  5. ^ "Dabrafenib/Trametinib Combination Approved for Advanced Melanoma". OncLive. January 9, 2013.
  6. ^ Maverakis E; Cornelius LA; Bowen GM; Phan T; Patel FB; Fitzmaurice S; He Y; Burrall B; Duong C; Kloxin AM; Sultani H; Wilken R; Martinez SR; Patel F (2015). "Metastatic melanoma – a review of current and future treatment options". Acta Derm Venereol. 95 (5): 516–524. doi:10.2340/00015555-2035. PMID 25520039.
  7. ^ 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". New England Journal of Medicine. 377 (19): 1813–1823. doi:10.1056/NEJMoa1708539. Retrieved 7 August 2018.
  8. ^ "FDA Approves Adjuvant Combo for BRAF+ Melanoma". www.medscape.com. WebMD LLC. Retrieved 2 May 2018.
  9. ^ Dabrafenib/Trametinib Combo Wins EU Approval for BRAF+ NSCLC. April 2017