Document Detail

A costly revolution for a subgroup of patients with metastatic melanoma.
MedLine Citation:
PMID:  23445310     Owner:  NLM     Status:  In-Data-Review    
ORIGINAL ARTICLE: Hauschild A, Grob JJ, Demidov LV et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380: 358-65. Background  Dabrafenib, an inhibitor of mutated BRAF, has clinical activity with a manageable safety profile in phase I and II studies in patients with BRAF (V600)-mutated metastatic melanoma. Hauschild et al. aimed to assess the efficacy of dabrafenib in a phase III trial of patients with BRAF (V600)-mutated metastatic melanoma. Methods  Patients were enrolled into a phase III trial between December 2010 and September 2011. This report is based on the cut-off date of 19 December 2011. Patients with previously untreated stage IV or unresectable stage III BRAF (V600)-mutated melanoma were randomly assigned (3:1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg m intravenously every 3 weeks). Patients were stratified according to American Joint Committee on Cancer stage. The primary endpoint was investigator-assessed progression-free survival (PFS) and was analysed by intention to treat. Safety was assessed per protocol. Findings  Of the 733 patients screened, 250 were randomly assigned to receive either dabrafenib (187 patients) or dacarbazine (63 patients). Median PFS was 5·1 months for dabrafenib and 2·7 months for dacarbazine, with a hazard ratio of 0·30 (95% confidence interval 0·18-0·51, P < 0·0001). At cut-off, 107 (57%) patients in the dabrafenib group and 14 (22%) in the dacarbazine group remained on randomized 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 effects were uncommon in both groups. Interpretation  Dabrafenib significantly improved PFS compared with dacarbazine.
A C J van Akkooi; T Nijsten
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The British journal of dermatology     Volume:  168     ISSN:  1365-2133     ISO Abbreviation:  Br. J. Dermatol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0004041     Medline TA:  Br J Dermatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  467-70     Citation Subset:  IM    
Copyright Information:
© 2013 The Authors. BJD © 2013 British Association of Dermatologists.
Department of Surgical Oncology, Erasmus University Medical Centre - Daniel den Hoed Cancer Centre, Rotterdam, the Netherlands Department of Dermatology, Erasmus University Medical Centre, Room GK-016, Burgemeester Jacobsplein 51, 3000 CA Rotterdam, the Netherlands E-mail:
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