TY - JOUR
T1 - Dabrafenib in BRAF-mutated metastatic melanoma
T2 - A multicentre, open-label, phase 3 randomised controlled trial
AU - Hauschild, Axel
AU - Grob, Jean Jacques
AU - Demidov, Lev V.
AU - Jouary, Thomas
AU - Gutzmer, Ralf
AU - Millward, Michael
AU - Rutkowski, Piotr
AU - Blank, Christian U.
AU - Miller, Wilson H.
AU - Kaempgen, Eckhart
AU - Martín-Algarra, Salvador
AU - Karaszewska, Boguslawa
AU - Mauch, Cornelia
AU - Chiarion-Sileni, Vanna
AU - Martin, Anne Marie
AU - Swann, Suzanne
AU - Haney, Patricia
AU - Mirakhur, Beloo
AU - Guckert, Mary E.
AU - Goodman, Vicki
AU - Chapman, Paul B.
PY - 2012/7
Y1 - 2012/7
N2 - 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 BRAFV600-mutated metastatic melanoma. We studied the efficacy of dabrafenib in patients with BRAFV600E-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 BRAFV600E mutation-positive melanoma were randomly assigned (3:1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg/m2 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
AB - 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 BRAFV600-mutated metastatic melanoma. We studied the efficacy of dabrafenib in patients with BRAFV600E-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 BRAFV600E mutation-positive melanoma were randomly assigned (3:1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg/m2 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
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U2 - 10.1016/S0140-6736(12)60868-X
DO - 10.1016/S0140-6736(12)60868-X
M3 - Article
C2 - 22735384
AN - SCOPUS:84864285704
SN - 0140-6736
VL - 380
SP - 358
EP - 365
JO - The Lancet
JF - The Lancet
IS - 9839
ER -