Trametinib (Mekinist)

General information

Class/mechanism: Reversible MEK1 (mitogen-activated extracellular signal regulated kinase 1) and MEK2 kinase inhibitor. MEK proteins are upstream and affect cellular proliferation by modulating the activity of the ERK (extracellular signal-related kinase) pathway. BRAF V600E mutations constitutively activate the BRAF pathway, which includes MEK1 and MEK2. By inhibiting MEK1 and MEK2, trametinib inhibits tumor cell growth that would otherwise be stimulated by constitutive activation from certain BRAF mutations.
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 used

• BRAF-mutated melanoma
• BRAF-mutated NSCLC
• BRAF-mutated anaplastic thyroid cancer
• BRAF-mutated tumors (disease-agnostic)

Patient drug information

• Trametinib (Mekinist) package insert

History of changes in FDA indication

Melanoma, BRAF-mutated

• 5/29/2013: FDA approved 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 METRIC)
• 1/10/2014: FDA approved in combination with Dabrafenib (Tafinlar) 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 and COMBI-MB)
• 4/30/2018: Regular FDA approval with Dabrafenib (Tafinlar) 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

• 6/22/2017: FDA approved in combination with Dabrafenib (Tafinlar) for patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test. (Based on BRF113928)

Thyroid cancer, BRAF-mutated

• 5/4/2018: FDA approval with Dabrafenib (Tafinlar) 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 BRF117019)

History of changes in EMA indication

• 6/30/2014: Initial marketing authorization as Mekinist

Also known as

• Code names: GSK-1120212, GSK1120212, JTP-74057
• Generic name: trametinib dimethyl sulfoxide
• Brand name: Mekinist, Meqsel