(ChemotherapyAdvisor) – Patients with BRAFV600E-mutated metastatic melanoma had significant improvement in progression-free survival (PFS) when treated with dabrafenib compared with dacarbazine, according to results of a randomized phase 3 study published in the Lancet online June 24.

The open-label BREAK-3 trial randomly assigned patients with previously untreated, stage IV metastatic or unresectable stage III BRAFV600E mutation-positive melanoma 3:1 to receive oral dabrafenib 150mg twice daily (n=187) or dacarbazine 1000mg/m2 IV every 3 weeks (n=63). Patients were enrolled between December 23, 2010 and September 1, 2011 from 70 sites in 12 countries.

At data cutoff on December 19, 2011, 107 patients (57%) in the dabrafenib group and 14 (22%) in the dacarbazine group remained on randomized treatment. Median PFS, the primary end point, was 5.1 months for dabrafenib and 2.7 months for dacarbazine (HR 0.30 [95% CI 0.18–0.51]; P<0.0001). In an independent review, 50% of patients treated with dabrafenib demonstrated a complete (3%; n=6) or partial response (47%; n=87) vs 7% of those treated with DTIC (2% complete response [n=1], 5% partial response [n=3]).

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Treatment-related adverse events (AEs) ≥grade 2 occurred in 100 of 187 patients (53%) treated with dabrafenib and in 26 of 59 patients (44%) who received dacarbazine. The most common AEs with dabrafenib were skin-related toxic effects, fever, fatigue, arthralgia, and headache and, with dacarbazine, nausea, vomiting, neutropenia, fatigue, and asthenia. Grade 3–4 adverse events were uncommon in both groups.

Approximately 50% of melanomas carry the mutated form of the BRAF gene. The investigators noted that compared with vemurafenib, side effects of dabrafenib affecting the skin are less severe than those experienced by patients who are treated with vemurafenib, an existing BRAF inhibitor recently approved by the US Food and Drug Administration.

The study was funded by GlaxoSmithKline.


Clinicaltrials.gov listing