Dabrafenib — Drug Monograph

Brand names: Tafinlar

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Selective, ATP-competitive inhibitor of BRAF kinase. Preferentially inhibits the V600E and V600K mutant forms of BRAF, blocking constitutive activation of the MAPK (RAS/RAF/MEK/ERK) signaling cascade that drives proliferation in BRAF-mutant cancers. Used in combination with trametinib (MEK inhibitor) to achieve more complete MAPK pathway suppression and delay resistance — single-agent BRAF inhibition causes paradoxical MEK/ERK activation in RAS-mutant cells (class effect), and combined BRAF + MEK inhibition prevents this rebound and improves outcomes.

FDA Indications

• Melanoma — BRAF V600E/K mutation-positive unresectable or metastatic (with trametinib)
• Melanoma — BRAF V600E/K, adjuvant after complete resection of Stage III (with trametinib)
• NSCLC — BRAF V600E mutation-positive metastatic (with trametinib)
• Anaplastic thyroid carcinoma (ATC) — BRAF V600E, locally advanced or metastatic (with trametinib — ROAR basket trial: 69% ORR, median OS 14.5 months)
• Solid tumors — BRAF V600E mutation-positive, unresectable or metastatic, after prior therapy, MSI-H/dMMR-negative or no satisfactory alternative (with trametinib — tumor-agnostic approval)
• Low-grade glioma (pediatric) — BRAF V600E mutation-positive (with trametinib)
• High-grade glioma (pediatric) — BRAF V600E mutation-positive (with trametinib)

Common Side Effects

• Pyrexia/fever (common; often requires dose interruption)
• Fatigue
• Hyperkeratosis (skin thickening)
• Headache
• Arthralgia
• Nausea
• Alopecia
• Rash
• Chills
• Diarrhea

Clinical Pearl

Dabrafenib should almost always be used in combination with trametinib (MEK inhibitor) — combination therapy dramatically reduces cuSCC risk (from ~20% to ~1%) and improves efficacy due to dual MAPK pathway blockade. Pyrexia (fever) is a class-specific toxicity of dabrafenib: manage with acetaminophen, consider corticosteroids for severe events, and interrupt dabrafenib (not trametinib) for Grade 3/4 fever. The combination is approved across tumor types in a tumor-agnostic indication for BRAF…

Related Therapies & Mechanisms

• Trametinib (Mekinist) — Tyrosine Kinase Inhibitor · NSCLC
• Larotrectinib (Vitrakvi) — Tyrosine Kinase Inhibitor · NSCLC
• Pralsetinib (Gavreto) — Tyrosine Kinase Inhibitor · NSCLC
• Selpercatinib (Retevmo) — Tyrosine Kinase Inhibitor · NSCLC