Dabrafenib selectively binds to and inhibits V600 mutant forms of the BRAF protein. BRAF is involved in the mitogen-activated protein kinase (MAPK) pathway, which regulates the normal growth and death of cells, including skin cells. Oncogenic mutations in BRAF lead to constitutive activation of this pathway and proliferation of tumour cells.1
The most commonly observed BRAF mutation is V600E, which accounts for approximately 90% of BRAF mutations seen in melanoma.1
In the phase III BREAK-3 trial, 250 patients with BRAF V600E mutation-positive unresectable or metastatic melanoma were randomised to receive dabrafenib or dacarbazine. The primary endpoint was progression-free survival (PFS).1
In the initial analysis (median follow-up time 4.9 months) a statistically significant improvement in PFS was observed in patients treated with dabrafenib compared with dacarbazine (HR 0.30, 95% CI 0.18–0.51; p<0.0001).1
In the updated analysis (median 10.5 months), a similar statistically significant improvement in median PFS was observed: 6.9 months in the dabrafenib arm compared with 2.7 months in the dacarbazine arm, (HR 0.37, 95% CI 0.24–0.58;p<0.0001). Median overall survival was 18.2 months for dabrafenib and 15.6 months for dacarbazine (HR.2
The most common adverse effects with dabrafenib were hyperkeratosis, headache, pyrexia, arthralgia, fatigue, nausea, vomiting, papilloma, alopecia and rash.1
- Tafinlar Summary of Product Characteristics, August 2013.
- Hauschild A et al. Presentation at Annual Meeting of the American Society of Clinical Oncology, Chicago, US, May-June 2013; abstract 9013.
Further information: GlaxoSmithKline