TY - JOUR
T1 - Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma
AU - Long, G.V.
AU - Hauschild, A.
AU - Santinami, M.
AU - Atkinson, V.
AU - Mandal, M.
AU - Chiarion-Sileni, V.
AU - Larkin, J.
AU - Nyakas, M.
AU - Dutriaux, C.
AU - Haydon, A.
AU - Robert, C.
AU - Mortier, L.
AU - Schachter, J.
AU - Schadendorf, D.
AU - Lesimple, T.
AU - Plummer, R.
AU - Ji, R.
AU - Zhang, P.
AU - Mookerjee, B.
AU - Legos, J.
AU - Kefford, R.
AU - Dummer, R.
AU - Kirkwood, J.M.
N1 - Cited By :13
Export Date: 22 February 2018
CODEN: NEJMA
Correspondence Address: Long, G.V.; Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals, 40 Rocklands Rd, Australia; email: georgina.long@sydney.edu.au
PY - 2017/11/9
Y1 - 2017/11/9
N2 - BACKGROUND Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. METHODS In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety. RESULTS At a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-Therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 to 0.58; P
AB - BACKGROUND Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. METHODS In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety. RESULTS At a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-Therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 to 0.58; P
U2 - 10.1056/NEJMoa1708539
DO - 10.1056/NEJMoa1708539
M3 - Article
VL - 377
SP - 1813
EP - 1823
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 19
ER -