Class: MEK inhibitor (targets MEK1 and MEK2, downstream of BRAF in the MAPK/ERK pathway).
Formulation: Oral tablet.
Indications (main ones in oncology practice)
- Metastatic melanoma with BRAF V600E or V600K mutation (as monotherapy or more commonly in combination with dabrafenib).
- Adjuvant treatment of stage III melanoma with BRAF V600E/K mutation after complete resection (with dabrafenib).
- NSCLC with BRAF V600E mutation (with dabrafenib).
- Anaplastic thyroid cancer with BRAF V600E mutation (with dabrafenib).
Dosing
- 2 mg orally once daily, taken on an empty stomach.
- Usually combined with dabrafenib (150 mg PO BID) for synergistic effect and to delay resistance.
Key Toxicities / Monitoring
- Cardiomyopathy → Monitor LVEF (echocardiogram/MUGA) at baseline, after 1 month, then q2–3 months.
- Ocular toxicity (retinal vein occlusion, retinal pigment epithelial detachment) → urgent ophthalmology exam if visual symptoms.
- Dermatologic reactions (rash, dermatitis, secondary skin malignancies).
- Interstitial lung disease (ILD)/pneumonitis.
- Hypertension → monitor BP regularly.
- Bleeding risk.
- Fever (particularly when combined with dabrafenib; may require drug hold and supportive care).
Drug Interactions
- Substrate of CYP3A4 and P-gp → caution with strong inducers/inhibitors.
- Avoid grapefruit juice.
Oncology pharmacist pearls:
- Always confirm BRAF V600E/K mutation before use.
- Trametinib should not be substituted for dabrafenib — they target different points in the MAPK pathway and are synergistic.
- Monitor cardiac and ocular function closely, and educate patients on fever management if on combo therapy.