Combined Vemurafenib and Combimetinib in BRAF-Mutated Melanoma

Larkin, James, Ascierto, Paolo, Dren, Brigette, Atkinson, Victoria, Liszkay, Gabriella, Maio, Michele, Mandala, Mario, Demidov, Lev, Stroyakovskiy, Daniil, Thomas, Luc, de la Cruz-Merino, Luis, Dutriaux, Caroline, Garbe, Claus, Sovak, Mika, Chang, Ilsung, Choong, Nicholas, Hack, Stephen, McArthur, Grant A. and Ribas, Antoni (2014) Combined Vemurafenib and Combimetinib in BRAF-Mutated Melanoma. The New England Journal of Medicine, 371 20: 1867-1876. doi:10.1056/NEJMoa1408868


Author Larkin, James
Ascierto, Paolo
Dren, Brigette
Atkinson, Victoria
Liszkay, Gabriella
Maio, Michele
Mandala, Mario
Demidov, Lev
Stroyakovskiy, Daniil
Thomas, Luc
de la Cruz-Merino, Luis
Dutriaux, Caroline
Garbe, Claus
Sovak, Mika
Chang, Ilsung
Choong, Nicholas
Hack, Stephen
McArthur, Grant A.
Ribas, Antoni
Title Combined Vemurafenib and Combimetinib in BRAF-Mutated Melanoma
Journal name The New England Journal of Medicine   Check publisher's open access policy
ISSN 0028-4793
1533-4406
Publication date 2014-11-13
Year available 2014
Sub-type Article (original research)
DOI 10.1056/NEJMoa1408868
Volume 371
Issue 20
Start page 1867
End page 1876
Total pages 10
Place of publication Waltham, MA United States
Publisher Massachusetts Medical Society
Collection year 2016
Language eng
Formatted abstract
Background The 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.

Methods
We 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.

Results
The 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
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Fri, 24 Jul 2015, 14:52:55 EST by Victoria Atkinson on behalf of Medicine - Princess Alexandra Hospital