Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FO - Dermatovenerologie

OECD FORD obor

—

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

New England Journal of Medicine

ISSN

0028-4793

e-ISSN

—

Svazek periodika

372

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

30-39

Kód UT WoS článku

000347100800007

EID výsledku v databázi Scopus

2-s2.0-84920394727