Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F15%3A10294490" target="_blank" >RIV/00064165:_____/15:10294490 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1056/NEJMoa1412690" target="_blank" >http://dx.doi.org/10.1056/NEJMoa1412690</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1056/NEJMoa1412690" target="_blank" >10.1056/NEJMoa1412690</a>
Alternative languages
Result language
angličtina
Original language name
Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib
Original language description
BACKGROUND The BRAF inhibitors vemurafenib and dabrafenib have shown efficacy as mono-therapies in patients with previously untreated metastatic melanoma with BRAF V600E or V600K mutations. Combining dabrafenib and the MEK inhibitor trametinib, as compared with dabrafenib alone, enhanced antitumor activity in this population of patients. METHODS In this open-label, phase 3 trial, we randomly assigned 704 patients with metastatic melanoma with a BRAF V600 mutation to receive either a combination of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) or vemurafenib (960 mg twice daily) orally as first-line therapy. The primary end point was overall survival. RESULTS At the preplanned interim overall survival analysis, which was performed after 77% of the total number of expected events occurred, the overall survival rate at 12 months was 72% (95% confidence interval [CI], 67 to 77) in the combination-therapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (hazard ratio for death in the combination-therapy group, 0.69; 95% CI, 0.53 to 0.89; P = 0.005). The prespecified interim stopping boundary was crossed, and the study was stopped for efficacy in July 2014. Median progression-free survival was 11.4 months in the combination-therapy group and 7.3 months in the vemurafenib group (hazard ratio, 0.56; 95% CI, 0.46 to 0.69; P< 0.001). The objective response rate was 64% in the combination-therapy group and 51% in the vemurafenib group (P< 0.001). Rates of severe adverse events and study-drug discontinuations were similar in the two groups. Cutaneous squamous-cell carcinoma and keratoacanthoma occurred in 1% of patients in the combination-therapy group and 18% of those in the vemurafenib group. CONCLUSIONS Dabrafenib plus trametinib, as compared with vemurafenib monotherapy, significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600K mutations, without increased overall toxicity.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FO - Dermatology and venereology
OECD FORD branch
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Result continuities
Project
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Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
New England Journal of Medicine
ISSN
0028-4793
e-ISSN
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Volume of the periodical
372
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
30-39
UT code for WoS article
000347100800007
EID of the result in the Scopus database
2-s2.0-84920394727