Related Experiment Video
Updated: May 21, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial
Axel Hauschild1, Jean-Jacques Grob, Lev V Demidov
1University Hospital, Schleswig-Holstein, Department of Dermatology, Kiel, Germany. ahauschild@dermatology.unikiel.de
Background:
Dabrafenib, an inhibitor of mutated BRAF, has clinical activity with a manageable safety profile in studies of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma. We studied the efficacy of dabrafenib in patients with BRAF(V600E)-mutated metastatic melanoma.
Methods:
We enrolled patients in this open-label phase 3 trial between Dec 23, 2010, and Sept 1, 2011. This report is based on a data cutoff date of Dec 19, 2011. Patients aged 18 years or older with previously untreated, stage IV or unresectable stage III BRAF(V600E) mutation-positive melanoma were randomly assigned (3:1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg/m(2) intravenously every 3 weeks). Patients were stratified according to American Joint Committee on Cancer stage (unresectable III+IVM1a+IVM1b vs IVM1c). The primary endpoint was investigator-assessed progression-free survival and was analysed by intention to treat; safety was assessed per protocol. This study is registered with ClinicalTrials.gov, number NCT01227889.
Findings:
Of the 733 patients screened, 250 were randomly assigned to receive either dabrafenib (187 patients) or dacarbazine (63 patients). Median progression-free survival was 5·1 months for dabrafenib and 2·7 months for dacarbazine, with a hazard ratio (HR) of 0·30 (95% CI 0·18-0·51; p<0·0001). At data cutoff, 107 (57%) patients in the dabrafenib group and 14 (22%) in the dacarbazine group remained on randomised treatment. Treatment-related adverse events (grade 2 or higher) occurred in 100 (53%) of the 187 patients who received dabrafenib and in 26 (44%) of the 59 patients who received dacarbazine. The most common adverse events with dabrafenib were skin-related toxic effects, fever, fatigue, arthralgia, and headache. The most common adverse events with dacarbazine were nausea, vomiting, neutropenia, fatigue, and asthenia. Grade 3-4 adverse events were uncommon in both groups.
Interpretation:
Dabrafenib significantly improved progression-free survival compared with dacarbazine.
Funding:
GlaxoSmithKline.
Insights
Dabrafenib significantly improved progression-free survival in patients with BRAF(V600E)-mutated melanoma compared to dacarbazine. This targeted therapy offers a new treatment option for advanced melanoma.
Area of Science:
- Oncology
- Medical research
Background:
- Dabrafenib is a BRAF inhibitor with demonstrated activity in phase 1 and 2 trials for BRAF(V600)-mutated metastatic melanoma.
- Previous studies indicated a manageable safety profile for dabrafenib.
Purpose of the Study:
- To evaluate the efficacy of dabrafenib in patients with BRAF(V600E)-mutated metastatic melanoma.
- To compare progression-free survival between dabrafenib and dacarbazine in this patient population.
Main Methods:
- An open-label, phase 3 randomized trial involving patients with previously untreated, stage IV or unresectable stage III BRAF(V600E) mutation-positive melanoma.
- Patients were assigned to receive either dabrafenib (150 mg twice daily) or dacarbazine (1000 mg/m(2) every 3 weeks) in a 3:1 ratio.
- The primary endpoint was investigator-assessed progression-free survival, analyzed by intention to treat.
Main Results:
- Median progression-free survival was 5.1 months for dabrafenib versus 2.7 months for dacarbazine (Hazard Ratio: 0.30; p<0.0001).
- Treatment-related adverse events (grade 2 or higher) were observed in 53% of dabrafenib recipients and 44% of dacarbazine recipients.
- Most common adverse events for dabrafenib included skin toxicities, fever, and fatigue; for dacarbazine, they included nausea, vomiting, and neutropenia.
Conclusions:
- Dabrafenib demonstrated a significant improvement in progression-free survival compared to dacarbazine.
- Dabrafenib represents an effective treatment option for patients with BRAF(V600E)-mutated metastatic melanoma.
