Annotation of European Medicines Agency (EMA) label information
for dabrafenib
and BRAF
Summary
Dabrafenib (Tafinlar) is indicated in adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation due to its mechanism of action as an inhibitor of RAF kinases. The EMA European Public Assessment Report (EPAR) states that testing for tumor BRAF V600 mutations is required as efficacy and safety of dabrafenib has not been established in patients with wildtype BRAF.
Annotation
Excerpts from the Dabrafenib (Tafinlar) EPAR:
Dabrafenib is an inhibitor of RAF kinases. Oncogenic mutations in BRAF lead to constitutive activation of the RAS/RAF/MEK/ERK pathway. BRAF mutations have been identified at a high frequency in specific cancers, including approximately 50% of melanoma. The most commonly observed BRAF mutation is V600E which accounts for approximately 90% of the BRAF mutations that are seen in melanoma.
Preclinical data generated in biochemical assays demonstrated that dabrafenib inhibits BRAF kinases with activating codon 600 mutations (Table 4).
Before taking dabrafenib, patients must have BRAF V600 mutation-positive tumour status confirmed by a validated test. In the Phase II and III clinical trials, screening for eligibility required central testing for BRAF V600 mutation using a BRAF mutation assay conducted on the most recent tumour sample available...Only subjects with BRAF V600E or V600K mutation positive tumors were eligible for study participation.
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Dabrafenib (Tafinlar) EMA drug label.
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