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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.[2] Dabrafenib acts as an inhibitor of the associated enzyme B-Raf, which plays a role in the regulation of cell growth.

Dabrafenib
Clinical data
Trade namesTafinlar
Other namesGSK-2118436
AHFS/Drugs.comMonograph
MedlinePlusa613038
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
  • N-{3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.215.965 Edit this at Wikidata
Chemical and physical data
FormulaC23H20F3N5O2S2
Molar mass519.56 g·mol−1
3D model (JSmol)
  • CC(C)(C)C1=NC(=C(S1)C2=NC(=NC=C2)N)C3=C(C(=CC=C3)NS(=O)(=O)C4=C(C=CC=C4F)F)F
  • InChI=1S/C23H20F3N5O2S2/c1-23(2,3)21-30-18(19(34-21)16-10-11-28-22(27)29-16)12-6-4-9-15(17(12)26)31-35(32,33)20-13(24)7-5-8-14(20)25/h4-11,31H,1-3H3,(H2,27,28,29)
  • Key:BFSMGDJOXZAERB-UHFFFAOYSA-N

The most common side effects include papilloma (warts), headache, nausea, vomiting, hyperkeratosis (thickening and toughening of the skin), hair loss, rash, joint pain, fever and tiredness.[3] When taken in combination with trametinib, the most common side effects include fever, tiredness, nausea, chills, headache, diarrhea, vomiting, joint pain and rash.[3]

Dabrafenib was approved for medical use in the United States in May 2013,[7] and in the European Union in August 2013.[3]

Medical uses

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Dabrafenib is indicated as a single agent for the treatment of people with unresectable or metastatic melanoma with BRAF V600E mutation.[2] Dabrafenib is indicated, in combination with trametinib, for BRAF V600E-positive unresectable or metastatic melanoma, metastatic non-small cell lung cancer, metastatic anaplastic thyroid cancer, and unresectable or metastatic solid tumors.[2][3][8]

History

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Clinical trial data demonstrated that resistance to dabrafenib and other BRAF inhibitors occurs within six to seven months.[9] To overcome this resistance, the BRAF inhibitor dabrafenib was combined with the MEK inhibitor trametinib.[9] In January 2014, the FDA approved this combination of dabrafenib and trametinib for BRAF V600E/K-mutant metastatic melanoma.[10][11] In 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,[12] making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma.[13]

Society and culture

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United States

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The US Food and Drug Administration (FDA) approved dabrafenib as a single agent treatment for people with BRAF V600E mutation-positive advanced melanoma in May 2013.[7][14]

European Union

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Dabrafenib was approved for use in the European Union in August 2013.[3]

In April 2017, the European Union approved the combination of dabrafenib with trametinib for BRAF V600-positive advanced or metastatic non small-cell lung cancer (NSCLC).[15][16][3]

In September 2023, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Finlee, intended for the treatment of low- and high-grade glioma (LGG and HGG).[17] The applicant for this medicinal product is Novartis Europharm Limited.[17] Finlee was approved for medical use in the European Union in November 2023.[4]

Brand names

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Dabrafenib is the international nonproprietary name.[18]

Dabrafenib is sold under the brand names Tafinlar[3] and Finlee.[4]

Research

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Dabrafenib has clinical activity with a manageable safety profile in clinical trials of phase I and II in patients with BRAF (V600)-mutated metastatic melanoma.[19][20]

References

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  1. ^ "Product monograph brand safety updates". Health Canada. February 2024. Retrieved March 24, 2024.
  2. ^ a b c d "Tafinlar- dabrafenib capsule". DailyMed. U.S. National Library of Medicine. June 22, 2022. Archived from the original on January 27, 2023. Retrieved January 27, 2023.
  3. ^ a b c d e f g h "Tafinlar EPAR". European Medicines Agency (EMA). September 17, 2018. Archived from the original on April 11, 2020. Retrieved April 10, 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. ^ a b c "Finlee EPAR". European Medicines Agency (EMA). November 15, 2023. Archived from the original on December 5, 2023. Retrieved December 10, 2023.
  5. ^ "Tafinlar Product information". Union Register of medicinal products. August 29, 2013. Archived from the original on January 11, 2023. Retrieved December 11, 2023.
  6. ^ "Finlee Product information". Union Register of medicinal products. November 16, 2023. Archived from the original on November 26, 2023. Retrieved December 11, 2023.
  7. ^ a b "Drug Approval Package: Tafinlar (dabrafenib) Capsules NDA #202806". U.S. Food and Drug Administration (FDA). December 24, 1999. Archived from the original on April 11, 2020. Retrieved April 10, 2020.
  8. ^ "FDA approves dabrafenib with trametinib for pediatric patients with low-grade glioma with a BRAF V600E mutation". U.S. Food and Drug Administration. March 16, 2023. Archived from the original on March 17, 2023. Retrieved March 17, 2023. Public Domain  This article incorporates text from this source, which is in the public domain.
  9. ^ a b Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, et al. (November 2012). "Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations". The New England Journal of Medicine. 367 (18): 1694–1703. doi:10.1056/NEJMoa1210093. PMC 3549295. PMID 23020132.
  10. ^ "Dabrafenib/Trametinib Combination Approved for Advanced Melanoma". OncLive. January 9, 2013. Archived from the original on January 25, 2014. Retrieved January 20, 2014.
  11. ^ Maverakis E, Cornelius LA, Bowen GM, Phan T, Patel FB, Fitzmaurice S, et al. (May 2015). "Metastatic melanoma - a review of current and future treatment options". Acta Dermato-Venereologica. 95 (5): 516–524. doi:10.2340/00015555-2035. PMID 25520039.
  12. ^ Long GV, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, et al. (November 2017). "Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma". The New England Journal of Medicine. 377 (19): 1813–1823. doi:10.1056/NEJMoa1708539. PMID 28891408. S2CID 205102412.
  13. ^ "FDA Approves Adjuvant Combo for BRAF+ Melanoma". www.medscape.com. WebMD LLC. Archived from the original on May 6, 2018. Retrieved May 2, 2018.
  14. ^ "GSK melanoma drugs add to tally of U.S. drug approvals". Reuters. May 30, 2013. Archived from the original on September 24, 2015. Retrieved December 10, 2023.
  15. ^ "EU Approves Dabrafenib/Trametinib Combination in BRAF+ NSCLC". Targeted Oncology. April 4, 2017. Archived from the original on January 27, 2021. Retrieved April 10, 2020.
  16. ^ "Mekinist EPAR". European Medicines Agency (EMA). September 17, 2018. Archived from the original on August 9, 2021. Retrieved April 10, 2020.
  17. ^ a b "Finlee: Pending EC decision". European Medicines Agency. September 15, 2023. Archived from the original on September 21, 2023. Retrieved September 21, 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  18. ^ World Health Organization (2012). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 67". WHO Drug Information. 26 (1): 45–96. hdl:10665/109416.
  19. ^ Gibney GT, Zager JS (July 2013). "Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies". Expert Opinion on Drug Metabolism & Toxicology. 9 (7): 893–899. doi:10.1517/17425255.2013.794220. PMID 23621583. S2CID 207491581.
  20. ^ Huang T, Karsy M, Zhuge J, Zhong M, Liu D (April 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.

Further reading

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