Dabrafenib (Tafinlar)

General information

Class/mechanism: BRAF kinase inhibitor. Dabrafenib inhibits some mutated BRAF kinases, such as BRAF V600E, BRAF V600K, and BRAF V600D. Some BRAF mutations such as BRAF V600E cause constitutive activation of the BRAF pathway, which drives tumor cell growth.
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp,UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is established (work in progress)

• Hairy cell leukemia
• Low-grade glioma, pediatric
• BRAF-mutated melanoma
• BRAF-mutated NSCLC
• BRAF-mutated anaplastic thyroid cancer

Diseases for which it is used

• BRAF-mutated colorectal cancer
• BRAF-mutated solid tumors (disease-agnostic)

Patient drug information

• Dabrafenib (Tafinlar) package insert
• Dabrafenib (Tafinlar) patient drug information (Chemocare)

History of changes in FDA indication

Low-grade glioma, pediatric

• 2023-03-16: FDA approved for pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy. (Based on TADPOLE)

Melanoma, BRAF-mutated

• 2013-05-29: FDA approved for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. (Based on BREAK-3 and BREAK-MB)
• 2014-01-10: Accelerated approval together with Trametinib (Mekinist) for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. (Based on COMBI-d, COMBI-v, and COMBI-MB)
• 2018-04-30: Regular FDA approval with Trametinib (Mekinist) in combination for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. (Based on COMBI-AD)

Non-small cell lung cancer, BRAF-mutated

• 2017-06-22: FDA approved in combination with Trametinib (Mekinist) for patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test. (Based on BRF113928 previously treated & BRF113928 untreated)

Thyroid cancer, BRAF-mutated

• 2018-05-04: FDA approval with Trametinib (Mekinist) in combination for the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options. (Based on ROAR)

History of changes in EMA indication

• 2013-08-26: Initial marketing authorization as Tafinlar.
• 2023-09-14: CHMP recommends authorization at Finlee. Finlee in combination with trametinib is indicated for the treatment of paediatric patients aged 1 year and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy.
• 2023-09-14: CHMP recommends authorization at Finlee. Finlee in combination with trametinib is indicated for the treatment of paediatric patients aged 1 year and older with high-grade glioma (HGG) with a BRAF V600E mutation who have received at least one prior radiation and/or chemotherapy treatment.

History of changes in Health Canada indication

Melanoma

• 2013-07-16: Initial notice of compliance as a monotherapy for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600 mutation.
• 2015-03-06: New indication with conditions in combination with trametinib for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600 mutation.
  • 2016-06-01: Conditions were met.
• 2018-09-21: New indication in combination with trametinib for the adjuvant treatment of patients with Stage III melanoma with a BRAF V600 mutation following resection.

Non-small cell lung cancer

• 2017-05-16: New indication in combination with trametinib for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600 mutation whose disease has progressed following systemic therapy.
• 2018-05-18: Expanded indication in combination with trametinib for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600 mutation.

History of changes in PMDA indication

• 2016-03-28: Initial approval for the treatment of unresectable melanoma with BRAF mutation.
• 2018-03-23: New additional indication and a new dosage indicated for the treatment of unresectable advanced or recurrent BRAF mutation-positive non-small cell lung cancer.
• 2018-07-02: New additional indication and a new dosage indicated for the treatment of BRAF mutation-positive melanoma.
• 2023-11-24: New indication and a new dosage for the treatment of advanced or recurrent BRAF mutation-positive solid tumor (excluding colon/rectal cancer) that is refractory or intolerant to standard therapies.
• 2023-11-24: New indication and a new dosage for the treatment of relapsed or refractory BRAF mutation-positive hairy cell leukemia.

Also known as

• Code names: GSK-2118436, GSK-2118436A
• Generic name: dabrafenib mesylate
• Brand name: Rafinlar, Tafinlar