Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial - PubMed (original) (raw)
Clinical Trial
. 2012 Jul 28;380(9839):358-65.
doi: 10.1016/S0140-6736(12)60868-X. Epub 2012 Jun 25.
Jean-Jacques Grob, Lev V Demidov, Thomas Jouary, Ralf Gutzmer, Michael Millward, Piotr Rutkowski, Christian U Blank, Wilson H Miller Jr, Eckhart Kaempgen, Salvador Martín-Algarra, Boguslawa Karaszewska, Cornelia Mauch, Vanna Chiarion-Sileni, Anne-Marie Martin, Suzanne Swann, Patricia Haney, Beloo Mirakhur, Mary E Guckert, Vicki Goodman, Paul B Chapman
Affiliations
- PMID: 22735384
- DOI: 10.1016/S0140-6736(12)60868-X
Clinical Trial
Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial
Axel Hauschild et al. Lancet. 2012.
Abstract
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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Comment in
- BRAF inhibition and beyond in advanced melanoma.
Margolin K. Margolin K. Lancet. 2012 Jul 28;380(9839):320-2. doi: 10.1016/S0140-6736(12)60993-3. Epub 2012 Jun 25. Lancet. 2012. PMID: 22735383 No abstract available. - A costly revolution for a subgroup of patients with metastatic melanoma.
van Akkooi AC, Nijsten T. van Akkooi AC, et al. Br J Dermatol. 2013 Mar;168(3):467-70; discussion 470-1. doi: 10.1111/bjd.12238. Br J Dermatol. 2013. PMID: 23445310 No abstract available.
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