Classification of Tafinlar (Dabrafenib) and Mekinist (Trametinib)
This regimen is targeted therapy, not immunotherapy or chemotherapy. Dabrafenib and trametinib are small-molecule kinase inhibitors that specifically target the MAPK signaling pathway in BRAF-mutated cancers 1.
Mechanism of Action
- Dabrafenib is an oral selective BRAF inhibitor that targets the BRAF V600E/K mutation, blocking constitutive activation of the MAPK pathway 1
- Trametinib is an oral MEK1 and MEK2 inhibitor that works downstream of BRAF in the same MAPK signal transduction pathway 1
- The combination provides dual blockade of the MAPK pathway, which regulates cellular proliferation, differentiation, survival, and apoptosis 1
Why This Is NOT Immunotherapy
The NCCN Guidelines explicitly distinguish this regimen from immunotherapy, stating "In contrast with immunotherapy, neoadjuvant therapy has not been studied in comparison with adjuvant dabrafenib and trametinib" 1. The guidelines note that anti-PD-1 options (true immunotherapy) are preferred, but if immunotherapy is contraindicated, dabrafenib and trametinib can be considered 1.
Why This Is NOT Chemotherapy
- Unlike cytotoxic chemotherapy agents (dacarbazine, paclitaxel), these drugs work through specific molecular targeting rather than general cell toxicity 1, 2
- Clinical trials directly compared this combination to traditional chemotherapy, demonstrating superior outcomes, confirming they are distinct therapeutic classes 1, 2
- The side effect profile differs markedly from chemotherapy—most common adverse events include pyrexia, chills, headache, rash, and diarrhea rather than typical chemotherapy toxicities like myelosuppression 1
Clinical Context
This combination is FDA-approved for BRAF V600E/K-mutated melanoma and other BRAF-mutated malignancies 1, 3. The standard dosing you mentioned (dabrafenib 150 mg twice daily and trametinib 2 mg once daily) is the approved regimen 1.