RT Journal Article
T1 Combined vemurafenib and cobimetinib in BRAF-mutated melanoma.
A1 Larkin, James
A1 Ascierto, Paolo A
A1 Dréno, Brigitte
A1 Atkinson, Victoria
A1 Liszkay, Gabriella
A1 Maio, Michele
A1 Mandalà, Mario
A1 Demidov, Lev
A1 Stroyakovskiy, Daniil
A1 Thomas, Luc
A1 de la Cruz-Merino, Luis
A1 Dutriaux, Caroline
A1 Garbe, Claus
A1 Sovak, Mika A
A1 Chang, Ilsung
A1 Choong, Nicholas
A1 Hack, Stephen P
A1 McArthur, Grant A
A1 Ribas, Antoni
K1 Indoles
K1 Sulfonamides
K1 Proto-oncogene proteins B-raf
K1 MAP quinasa quinasa 1
K1 Azetidines
K1 Piperidinas
K1 Sulfonamidas
K1 Azetidinas
AB BACKGROUNDThe combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib.METHODSWe randomly assigned 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemurafenib and placebo (control group). The primary end point was investigator-assessed progression-free survival.RESULTSThe median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval [CI], 0.39 to 0.68; P<0.001). The rate of complete or partial response in the combination group was 68%, as compared with 45% in the control group (P<0.001), including rates of complete response of 10% in the combination group and 4% in the control group. Progression-free survival as assessed by independent review was similar to investigator-assessed progression-free survival. Interim analyses of overall survival showed 9-month survival rates of 81% (95% CI, 75 to 87) in the combination group and 73% (95% CI, 65 to 80) in the control group. Vemurafenib and cobimetinib was associated with a nonsignificantly higher incidence of adverse events of grade 3 or higher, as compared with vemurafenib and placebo (65% vs. 59%), and there was no significant difference in the rate of study-drug discontinuation. The number of secondary cutaneous cancers decreased with the combination therapy.CONCLUSIONSThe addition of cobimetinib to vemurafenib was associated with a significant improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma, at the cost of some increase in toxicity. (Funded by F. Hoffmann-La Roche/Genentech; coBRIM ClinicalTrials.gov number, NCT01689519.).
PB Massachusetts Medical Society
SN 0028-4793
YR 2014
FD 2014-11-13
LK http://hdl.handle.net/10668/2159
UL http://hdl.handle.net/10668/2159
LA en
NO Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N. Engl. J. Med.. 2014 ; 371(20):1867-76
NO Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 12, 2025