Dabrafenib Explained

Width:200
Tradename:Tafinlar
Dailymedid:Dabrafenib
Routes Of Administration:By mouth
Atc Prefix:L01
Atc Suffix:EC02
Legal Au:S4
Legal Ca:Rx-only
Legal Ca Comment:[1]
Legal Us:Rx-only
Legal Us Comment:[2]
Legal Eu:Rx-only
Legal Eu Comment:[3] [4]
Legal Status:Rx-only
Cas Number:1195765-45-7
Pubchem:44462760
Drugbank:DB08912
Chemspiderid:25948204
Kegg:D10064
Unii:QGP4HA4G1B
Chebi:75045
Chembl:2028663
Pdb Ligand:P06
Synonyms:GSK-2118436
Iupac Name:N--2,6-difluorobenzenesulfonamide
C:23
H:20
F:3
N:5
O:2
S:2
Smiles: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
Stdinchi: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)
Stdinchikey:BFSMGDJOXZAERB-UHFFFAOYSA-N

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

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. When taken in combination with trametinib, the most common side effects include fever, tiredness, nausea, chills, headache, diarrhea, vomiting, joint pain and rash.

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

Medical uses

Dabrafenib is indicated as a single agent for the treatment of people with unresectable or metastatic melanoma with BRAF V600E mutation. 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.[5]

History

Clinical trial data demonstrated that resistance to dabrafenib and other BRAF inhibitors occurs within six to seven months.[6] To overcome this resistance, the BRAF inhibitor dabrafenib was combined with the MEK inhibitor trametinib. In January 2014, the FDA approved this combination of dabrafenib and trametinib for BRAF V600E/K-mutant metastatic melanoma.[7] [8] 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,[9] making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma.[10]

Society and culture

Legal status

United States

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.[11] [12]

European Union

Dabrafenib was approved for use in the European Union in August 2013.[13]

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).[14] [15]

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). The applicant for this medicinal product is Novartis Europharm Limited.[16] Finlee was approved for medical use in the European Union in November 2023.[17]

Brand names

Dabrafenib is the international nonproprietary name.[18]

Dabrafenib is sold under the brand names Tafinlar and Finlee.

Research

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]

Further reading

Notes and References

  1. Web site: Product monograph brand safety updates . Health Canada . February 2024 . 24 March 2024.
  2. Web site: Tafinlar- dabrafenib capsule . DailyMed . U.S. National Library of Medicine . June 22, 2022 . January 27, 2023 . January 27, 2023 . https://web.archive.org/web/20230127060100/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fee1e6b1-e1a5-4254-9f2e-a70e0f8dbdea . live .
  3. Web site: Tafinlar Product information . Union Register of medicinal products . 29 August 2013 . 11 December 2023 . January 11, 2023 . https://web.archive.org/web/20230111211302/https://ec.europa.eu/health/documents/community-register/html/h865.htm . live .
  4. Web site: Finlee Product information . Union Register of medicinal products . 16 November 2023 . 11 December 2023 . November 26, 2023 . https://web.archive.org/web/20231126162554/https://ec.europa.eu/health/documents/community-register/html/h1767.htm . live .
  5. Web site: 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 . March 17, 2023 . March 17, 2023 . https://web.archive.org/web/20230317150821/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-dabrafenib-trametinib-pediatric-patients-low-grade-glioma-braf-v600e-mutation . live .
  6. Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, Hamid O, Schuchter L, Cebon J, Ibrahim N, Kudchadkar R, Burris HA, Falchook G, Algazi A, Lewis K, Long GV, Puzanov I, Lebowitz P, Singh A, Little S, Sun P, Allred A, Ouellet D, Kim KB, Patel K, Weber J . Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations . The New England Journal of Medicine . 367 . 18 . 1694–1703 . November 2012 . 23020132 . 3549295 . 10.1056/NEJMoa1210093 .
  7. News: Dabrafenib/Trametinib Combination Approved for Advanced Melanoma . OncLive . January 9, 2013 . January 20, 2014 . January 25, 2014 . https://web.archive.org/web/20140125190539/http://www.onclive.com/web-exclusives/FDA-Approves-First-Ever-Combination-for-Metastatic-Melanoma . live .
  8. 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 . Metastatic melanoma - a review of current and future treatment options . Acta Dermato-Venereologica . 95 . 5 . 516–524 . May 2015 . 25520039 . 10.2340/00015555-2035 . free .
  9. Long GV, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, Larkin J, Nyakas M, Dutriaux C, Haydon A, Robert C, Mortier L, Schachter J, Schadendorf D, Lesimple T, Plummer R, Ji R, Zhang P, Mookerjee B, Legos J, Kefford R, Dummer R, Kirkwood JM . Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma . The New England Journal of Medicine . 377 . 19 . 1813–1823 . November 2017 . 28891408 . 10.1056/NEJMoa1708539 . 205102412 . Georgina Long . free .
  10. Web site: FDA Approves Adjuvant Combo for BRAF+ Melanoma. www.medscape.com. WebMD LLC. May 2, 2018. May 6, 2018. https://web.archive.org/web/20180506065323/https://www.medscape.com/viewarticle/895984. live.
  11. Web site: Drug Approval Package: Tafinlar (dabrafenib) Capsules NDA #202806 . U.S. Food and Drug Administration (FDA) . December 24, 1999 . April 10, 2020 . April 11, 2020 . https://web.archive.org/web/20200411062834/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/202806Orig1s000TOC.cfm . live .
  12. News: GSK melanoma drugs add to tally of U.S. drug approvals . Reuters . May 30, 2013 . December 10, 2023 . September 24, 2015 . https://web.archive.org/web/20150924181713/http://www.reuters.com/article/2013/05/30/us-glaxosmithkline-approvals-idUSBRE94S1A020130530 . live .
  13. Web site: Tafinlar EPAR . European Medicines Agency (EMA) . September 17, 2018 . April 10, 2020 . April 11, 2020 . https://web.archive.org/web/20200411062833/https://www.ema.europa.eu/en/medicines/human/EPAR/tafinlar . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  14. Web site: EU Approves Dabrafenib/Trametinib Combination in BRAF+ NSCLC . Targeted Oncology . April 4, 2017 . April 10, 2020 . January 27, 2021 . https://web.archive.org/web/20210127045636/https://www.targetedonc.com/view/eu-approves-dabrafenibtrametinib-combination-in-braf-nsclc . live .
  15. Web site: Mekinist EPAR . European Medicines Agency (EMA) . September 17, 2018 . April 10, 2020 . August 9, 2021 . https://web.archive.org/web/20210809155109/https://www.ema.europa.eu/en/medicines/human/EPAR/mekinist . live .
  16. Web site: Finlee: Pending EC decision . European Medicines Agency . September 15, 2023 . September 21, 2023 . September 21, 2023 . https://web.archive.org/web/20230921045854/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/finlee . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  17. Web site: Finlee EPAR . European Medicines Agency (EMA) . November 15, 2023 . December 10, 2023 . December 5, 2023 . https://web.archive.org/web/20231205183018/https://www.ema.europa.eu/en/medicines/human/EPAR/finlee . live .
  18. ((World Health Organization)) . 2012 . International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 67 . WHO Drug Information . 26 . 1 . 10665/109416 . free . World Health Organization . 45–96 .
  19. Gibney GT, Zager JS . Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies . Expert Opinion on Drug Metabolism & Toxicology . 9 . 7 . 893–899 . July 2013 . 23621583 . 10.1517/17425255.2013.794220 . 207491581 .
  20. Huang T, Karsy M, Zhuge J, Zhong M, Liu D . B-Raf and the inhibitors: from bench to bedside . Journal of Hematology & Oncology . 6 . 30 . April 2013 . 23617957 . 3646677 . 10.1186/1756-8722-6-30 . free .

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