Dabrafenib

{{Short description|Anti-cancer medication}} {{Use mdy dates|date=February 2025}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | image = Dabrafenib.svg | image_class = skin-invert-image | image2 = Dabrafenib-from-xtal-3D-bs-17.png | image_class2 = bg-transparent | width = 200 | alt = | alt2 = | caption =

| tradename = Tafinlar | Drugs.com = {{drugs.com|monograph|dabrafenib-mesylate}} | MedlinePlus = a613038 | DailyMedID = Dabrafenib | pregnancy_AU =  | pregnancy_category = | routes_of_administration = By mouth | ATCvet = | ATC_prefix = L01 | ATC_suffix = EC02

| legal_AU = S4 | legal_AU_comment = | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=Health Canada | date=February 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=March 24, 2024}}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Tafinlar FDA label">{{cite web | title=Tafinlar- dabrafenib capsule | work=DailyMed | publisher=U.S. National Library of Medicine | date=June 22, 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fee1e6b1-e1a5-4254-9f2e-a70e0f8dbdea | access-date=January 27, 2023 | archive-date=January 27, 2023 | archive-url=https://web.archive.org/web/20230127060100/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fee1e6b1-e1a5-4254-9f2e-a70e0f8dbdea | url-status=live }}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Tafinlar EPAR" /><ref name="Finlee EPAR" /><ref>{{cite web | title=Tafinlar Product information | website=Union Register of medicinal products | date=August 29, 2013 | url=https://ec.europa.eu/health/documents/community-register/html/h865.htm | access-date=December 11, 2023 | archive-date=January 11, 2023 | archive-url=https://web.archive.org/web/20230111211302/https://ec.europa.eu/health/documents/community-register/html/h865.htm | url-status=live }}</ref><ref>{{cite web | title=Finlee Product information | website=Union Register of medicinal products | date=November 16, 2023 | url=https://ec.europa.eu/health/documents/community-register/html/h1767.htm | access-date=December 11, 2023 | archive-date=November 26, 2023 | archive-url=https://web.archive.org/web/20231126162554/https://ec.europa.eu/health/documents/community-register/html/h1767.htm | url-status=live }}</ref> | legal_UN =  | legal_UN_comment = | legal_status = Rx-only

| IUPAC_name = ''N''-{3-[5-(2-aminopyrimidin-4-yl)-2-''tert''-butyl-1,3-thiazol-4-yl]-2-fluorophenyl}-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.<ref name="Tafinlar FDA label" /> 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.<ref name="Tafinlar EPAR" /> When taken in combination with trametinib, the most common side effects include fever, tiredness, nausea, chills, headache, diarrhea, vomiting, joint pain and rash.<ref name="Tafinlar EPAR" />

Dabrafenib was approved for medical use in the United States in May 2013,<ref name="Tafinlar FDA approval package" /> and in the European Union in August 2013.<ref name="Tafinlar EPAR" />

== Medical uses == Dabrafenib is indicated as a single agent for the treatment of people with unresectable or metastatic melanoma with BRAF V600E mutation.<ref name="Tafinlar FDA label" /> 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.<ref name="Tafinlar FDA label" /><ref name="Tafinlar EPAR" /><ref>{{cite web | title=FDA approves dabrafenib with trametinib for pediatric patients with low-grade glioma with a BRAF V600E mutation | website=U.S. Food and Drug Administration | date=March 16, 2023 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-dabrafenib-trametinib-pediatric-patients-low-grade-glioma-braf-v600e-mutation | access-date=March 17, 2023 | archive-date=March 17, 2023 | archive-url=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 }} {{PD-notice}}</ref>

== History == Clinical trial data demonstrated that resistance to dabrafenib and other BRAF inhibitors occurs within six to seven months.<ref name="NEJM">{{cite journal | vauthors = 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 | title = Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations | journal = The New England Journal of Medicine | volume = 367 | issue = 18 | pages = 1694–1703 | date = November 2012 | pmid = 23020132 | pmc = 3549295 | doi = 10.1056/NEJMoa1210093 }}</ref> To overcome this resistance, the BRAF inhibitor dabrafenib was combined with the MEK inhibitor trametinib.<ref name="NEJM" /> In January 2014, the FDA approved this combination of dabrafenib and trametinib for BRAF V600E/K-mutant metastatic melanoma.<ref>{{cite news | url = http://www.onclive.com/web-exclusives/FDA-Approves-First-Ever-Combination-for-Metastatic-Melanoma | title = Dabrafenib/Trametinib Combination Approved for Advanced Melanoma | publisher = OncLive | date = January 9, 2013 | access-date = January 20, 2014 | archive-date = January 25, 2014 | archive-url = https://web.archive.org/web/20140125190539/http://www.onclive.com/web-exclusives/FDA-Approves-First-Ever-Combination-for-Metastatic-Melanoma | url-status = live }}</ref><ref>{{cite journal | vauthors = 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 | title = Metastatic melanoma - a review of current and future treatment options | journal = Acta Dermato-Venereologica | volume = 95 | issue = 5 | pages = 516–524 | date = May 2015 | pmid = 25520039 | doi = 10.2340/00015555-2035 | doi-access = free }}</ref> 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,<ref name="Long et al">{{cite journal | vauthors = 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 | title = Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma | journal = The New England Journal of Medicine | volume = 377 | issue = 19 | pages = 1813–1823 | date = November 2017 | pmid = 28891408 | doi = 10.1056/NEJMoa1708539 | s2cid = 205102412 | author-link1 = Georgina Long | doi-access = free }}</ref> making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma.<ref name="Medscape">{{cite web|title=FDA Approves Adjuvant Combo for BRAF+ Melanoma|url=https://www.medscape.com/viewarticle/895984|website=www.medscape.com|publisher=WebMD LLC|access-date=May 2, 2018|archive-date=May 6, 2018|archive-url=https://web.archive.org/web/20180506065323/https://www.medscape.com/viewarticle/895984|url-status=live}}</ref>

== 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.<ref name="Tafinlar FDA approval package">{{cite web | title=Drug Approval Package: Tafinlar (dabrafenib) Capsules NDA #202806 | website=U.S. Food and Drug Administration (FDA) | date=December 24, 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/202806Orig1s000TOC.cfm | access-date=April 10, 2020 | archive-date=April 11, 2020 | archive-url=https://web.archive.org/web/20200411062834/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/202806Orig1s000TOC.cfm }}</ref><ref>{{cite news | url = https://www.reuters.com/article/us-glaxosmithkline-approvals-idUSBRE94S1A020130530 | title = GSK melanoma drugs add to tally of U.S. drug approvals | publisher = Reuters | date = May 30, 2013 | access-date = December 10, 2023 | archive-date = September 24, 2015 | archive-url = https://web.archive.org/web/20150924181713/http://www.reuters.com/article/2013/05/30/us-glaxosmithkline-approvals-idUSBRE94S1A020130530 | url-status = live }}</ref>

==== European Union ==== Dabrafenib was approved for use in the European Union in August 2013.<ref name="Tafinlar EPAR">{{cite web | title=Tafinlar EPAR | website=European Medicines Agency (EMA) | date=September 17, 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/tafinlar | access-date=April 10, 2020 | archive-date=April 11, 2020 | archive-url=https://web.archive.org/web/20200411062833/https://www.ema.europa.eu/en/medicines/human/EPAR/tafinlar | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>

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).<ref>{{cite web | title=EU Approves Dabrafenib/Trametinib Combination in BRAF+ NSCLC | website=Targeted Oncology | date=April 4, 2017 | url=https://www.targetedonc.com/view/eu-approves-dabrafenibtrametinib-combination-in-braf-nsclc | access-date=April 10, 2020 | archive-date=January 27, 2021 | archive-url=https://web.archive.org/web/20210127045636/https://www.targetedonc.com/view/eu-approves-dabrafenibtrametinib-combination-in-braf-nsclc | url-status=live }}</ref><ref>{{cite web | title=Mekinist EPAR | website=European Medicines Agency (EMA) | date=September 17, 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/mekinist | access-date=April 10, 2020 | archive-date=August 9, 2021 | archive-url=https://web.archive.org/web/20210809155109/https://www.ema.europa.eu/en/medicines/human/EPAR/mekinist | url-status=live }}</ref><ref name="Tafinlar EPAR" />

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).<ref name="Finlee: Pending EC decision" /> The applicant for this medicinal product is Novartis Europharm Limited.<ref name="Finlee: Pending EC decision">{{cite web | title=Finlee: Pending EC decision | website=European Medicines Agency | date=September 15, 2023 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/finlee | access-date=September 21, 2023 | archive-date=September 21, 2023 | archive-url=https://web.archive.org/web/20230921045854/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/finlee | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Finlee was approved for medical use in the European Union in November 2023.<ref name="Finlee EPAR">{{cite web | title=Finlee EPAR | website=European Medicines Agency (EMA) | date=November 15, 2023 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/finlee | access-date=December 10, 2023 | archive-date=December 5, 2023 | archive-url=https://web.archive.org/web/20231205183018/https://www.ema.europa.eu/en/medicines/human/EPAR/finlee | url-status=live }}</ref>

=== Brand names === Dabrafenib is the international nonproprietary name.<ref>{{cite journal | year = 2012 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 67 | journal = WHO Drug Information | volume = 26 | issue = 1 | hdl = 10665/109416 | hdl-access = free | pages = 45–96 }}</ref>

Dabrafenib is sold under the brand names Tafinlar<ref name="Tafinlar EPAR" /> and Finlee.<ref name="Finlee EPAR" />

== 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.<ref>{{cite journal | vauthors = Gibney GT, Zager JS | title = Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 9 | issue = 7 | pages = 893–899 | date = July 2013 | pmid = 23621583 | doi = 10.1517/17425255.2013.794220 | s2cid = 207491581 }}</ref><ref>{{cite journal | vauthors = Huang T, Karsy M, Zhuge J, Zhong M, Liu D | title = B-Raf and the inhibitors: from bench to bedside | journal = Journal of Hematology & Oncology | volume = 6 | article-number = 30 | date = April 2013 | pmid = 23617957 | pmc = 3646677 | doi = 10.1186/1756-8722-6-30 | doi-access = free }}</ref>

== References == {{reflist}}

== Further reading == {{refbegin}} * {{cite book | title=Medical Genetics Summaries | chapter=Dabrafenib Therapy and BRAF and G6PD Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK447415/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | publisher=National Center for Biotechnology Information (NCBI) | year=2017 | pmid=28809523 | id=Bookshelf ID: NBK447415 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ | access-date=February 5, 2020 | archive-date=October 26, 2020 | archive-url=https://web.archive.org/web/20201026145821/https://www.ncbi.nlm.nih.gov/books/NBK61999/ | url-status=live }} {{refend}}

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Category:Aminopyrimidines Category:Chemotherapy Category:CYP3A4 inducers Category:Sulfonamides Category:Thiazoles Category:Organofluorides Category:B-Raf inhibitors Category:Tert-butyl compounds Category:Fluoroarenes Category:Drugs developed by Novartis Category:Enzyme inhibitors Category:Orphan drugs