Five-year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K-mutant advanced or metastatic melanoma.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Brain Neoplasms
/ drug therapy
Dacarbazine
/ administration & dosage
Female
Follow-Up Studies
Humans
Male
Melanoma
/ drug therapy
Middle Aged
Mutation
Paclitaxel
/ administration & dosage
Prognosis
Proto-Oncogene Proteins B-raf
/ genetics
Pyridones
/ administration & dosage
Pyrimidinones
/ administration & dosage
Skin Neoplasms
/ drug therapy
Survival Rate
Time Factors
Young Adult
Melanoma, Cutaneous Malignant
MEK inhibitor
METRIC
Survival
Targeted therapy
Trametinib
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
21
11
2018
revised:
30
11
2018
accepted:
05
12
2018
pubmed:
29
1
2019
medline:
22
5
2020
entrez:
29
1
2019
Statut:
ppublish
Résumé
Primary findings from the METRIC (TMT212A2301) study demonstrated that trametinib improved progression-free survival (PFS) and overall survival (OS) compared with chemotherapy in patients with unresectable or metastatic cutaneous melanoma with a BRAF V600 E/K mutation. However, clinical data characterising the long-term use of these therapies in combination with BRAF inhibitors or as monotherapies are limited. In this open-label, phase 3 study, 322 patients with BRAF V600 E/K-mutant metastatic melanoma were randomised in a 2:1 ratio to receive trametinib (2 mg orally, once daily; n = 214) or chemotherapy (dacarbazine [1000 mg/m The median PFS was 4.9 months in the trametinib arm versus 1.5 months in the chemotherapy arm (hazard ratio, 0.54; 95% confidence interval, 0.41-0.73). Landmark OS rates for trametinib versus chemotherapy arms at 1 year, 2 years and 5 years were 60.9% versus 49.6%, 32.0% versus 29.4% and 13.3% versus 17.0%, respectively. Most patients (n = 70 [65%]) from the chemotherapy arm crossed over to the trametinib arm early in their treatment. No unexpected adverse events were reported. This 5-year follow-up of patients with BRAF V600 E/K-mutant metastatic melanoma on a targeted therapy demonstrates that long-term use of trametinib is possible with no new or unexpected adverse events. Some patients experienced long-term survival benefit with trametinib monotherapy (METRIC ClinicalTrials.gov number, NCT01245062.).
Sections du résumé
BACKGROUND
Primary findings from the METRIC (TMT212A2301) study demonstrated that trametinib improved progression-free survival (PFS) and overall survival (OS) compared with chemotherapy in patients with unresectable or metastatic cutaneous melanoma with a BRAF V600 E/K mutation. However, clinical data characterising the long-term use of these therapies in combination with BRAF inhibitors or as monotherapies are limited.
METHODS
In this open-label, phase 3 study, 322 patients with BRAF V600 E/K-mutant metastatic melanoma were randomised in a 2:1 ratio to receive trametinib (2 mg orally, once daily; n = 214) or chemotherapy (dacarbazine [1000 mg/m
RESULTS
The median PFS was 4.9 months in the trametinib arm versus 1.5 months in the chemotherapy arm (hazard ratio, 0.54; 95% confidence interval, 0.41-0.73). Landmark OS rates for trametinib versus chemotherapy arms at 1 year, 2 years and 5 years were 60.9% versus 49.6%, 32.0% versus 29.4% and 13.3% versus 17.0%, respectively. Most patients (n = 70 [65%]) from the chemotherapy arm crossed over to the trametinib arm early in their treatment. No unexpected adverse events were reported.
CONCLUSIONS
This 5-year follow-up of patients with BRAF V600 E/K-mutant metastatic melanoma on a targeted therapy demonstrates that long-term use of trametinib is possible with no new or unexpected adverse events. Some patients experienced long-term survival benefit with trametinib monotherapy (METRIC ClinicalTrials.gov number, NCT01245062.).
Identifiants
pubmed: 30690294
pii: S0959-8049(18)31561-2
doi: 10.1016/j.ejca.2018.12.015
pii:
doi:
Substances chimiques
Pyridones
0
Pyrimidinones
0
trametinib
33E86K87QN
Dacarbazine
7GR28W0FJI
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Paclitaxel
P88XT4IS4D
Banques de données
ClinicalTrials.gov
['NCT01245062']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
61-69Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.