Class: Oral selective BRAF inhibitor (kinase inhibitor)
Mechanism of Action
- Inhibits mutant BRAF V600E and V600K kinases, blocking downstream MAPK/ERK pathway → ↓ tumor cell proliferation.
- Not active in wild-type BRAF tumors (can paradoxically activate MAPK and stimulate tumor growth).
Approved Indications
- Melanoma (unresectable or metastatic, BRAF V600E/K mutation) – as monotherapy or with trametinib.
- Adjuvant treatment of melanoma (resected Stage III, BRAF V600E/K mutation) – with trametinib.
- NSCLC (metastatic, BRAF V600E mutation) – with trametinib.
- Anaplastic thyroid carcinoma (ATC) (BRAF V600E mutation, unresectable/metastatic, no satisfactory local options) – with trametinib.
Dosing (Adults)
- 150 mg PO twice daily (capsules, take on empty stomach)
- Always confirm BRAF mutation status before initiation
- Commonly combined with trametinib 2 mg PO once daily for better efficacy and less cutaneous toxicity.
Toxicities & Monitoring
Common:
- Pyrexia (very frequent, may require dose interruption)
- Fatigue, headache, arthralgia, rash, hyperkeratosis, alopecia
- Nausea, vomiting, diarrhea, decreased appetite
Serious:
- Cutaneous malignancies (squamous cell carcinoma, keratoacanthoma, new primary melanoma) → dermatologic exams q2 months
- Febrile reactions (can be severe, with rigors, hypotension, renal impairment)
- Cardiomyopathy (↓ LVEF, esp. with trametinib) → baseline & periodic echocardiogram
- Hyperglycemia (monitor in diabetics)
- Ocular toxicity (uveitis, retinal vein occlusion, retinal pigment epithelial detachment)
- QT prolongation (rare; baseline ECG/electrolytes if risk)
Drug Interactions
- Substrate of CYP2C8 and CYP3A4
- Moderate CYP3A4 and CYP2C9 inducer → can ↓ levels of warfarin, hormonal contraceptives, some statins
- Avoid strong CYP3A4 inhibitors/inducers if possible
- Take at least 1 hour before or 2 hours after food
Clinical Pearls for Pharmacists
- Combination dabrafenib + trametinib is standard of care (synergistic efficacy, less skin toxicity vs monotherapy).
- Manage fever aggressively: hold therapy, antipyretics, short-course corticosteroids if severe or recurrent.
- Educate patients to report new skin lesions, fever, vision changes, or cardiac symptoms promptly.
- Avoid in wild-type BRAF tumors (can worsen cancer).
In practice:
- Melanoma: frontline in BRAF-mutant disease (often combined with immunotherapy in sequencing strategies).
- NSCLC & ATC: used only if confirmed BRAF V600E mutation present.