Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAF
Adult
Aged
Antibodies, Monoclonal, Humanized
/ adverse effects
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Azetidines
/ adverse effects
Double-Blind Method
Drug Administration Schedule
Female
Humans
Kaplan-Meier Estimate
Male
Melanoma
/ drug therapy
Middle Aged
Mutation
Neoplasm Metastasis
Neoplasm Staging
Piperidines
/ adverse effects
Progression-Free Survival
Proto-Oncogene Proteins B-raf
/ genetics
Vemurafenib
/ adverse effects
Journal
Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R
Informations de publication
Date de publication:
13 06 2020
13 06 2020
Historique:
received:
02
03
2020
revised:
02
04
2020
accepted:
14
04
2020
entrez:
15
6
2020
pubmed:
15
6
2020
medline:
24
6
2020
Statut:
ppublish
Résumé
IMspire150 aimed to evaluate first-line combination treatment with BRAF plus MEK inhibitors and immune checkpoint therapy in BRAF IMspire150 was a randomised, double-blind, placebo-controlled phase 3 study done at 112 institutes in 20 countries. Patients with unresectable stage IIIc-IV, BRAF Between Jan 13, 2017, and April 26, 2018, 777 patients were screened and 514 were enrolled and randomly assigned to the atezolizumab group (n=256) or control group (n=258). At a median follow-up of 18·9 months (IQR 10·4-23·8), progression-free survival as assessed by the study investigator was significantly prolonged with atezolizumab versus control (15·1 vs 10·6 months; hazard ratio [HR] 0·78; 95% CI 0·63-0·97; p=0·025). Common treatment-related adverse events (>30%) in the atezolizumab and control groups were blood creatinine phosphokinase increased (51·3% vs 44·8%), diarrhoea (42·2% vs 46·6%), rash (40·9%, both groups), arthralgia (39·1% vs 28·1%), pyrexia (38·7% vs 26·0%), alanine aminotransferase increased (33·9% vs 22·8%), and lipase increased (32·2% vs 27·4%); 13% of patients in the atezolizumab group and 16% in the control group stopped all treatment because of adverse events. The addition of atezolizumab to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and significantly increased progression-free survival in patients with BRAF F Hoffmann-La Roche and Genentech.
Sections du résumé
BACKGROUND
IMspire150 aimed to evaluate first-line combination treatment with BRAF plus MEK inhibitors and immune checkpoint therapy in BRAF
METHODS
IMspire150 was a randomised, double-blind, placebo-controlled phase 3 study done at 112 institutes in 20 countries. Patients with unresectable stage IIIc-IV, BRAF
FINDINGS
Between Jan 13, 2017, and April 26, 2018, 777 patients were screened and 514 were enrolled and randomly assigned to the atezolizumab group (n=256) or control group (n=258). At a median follow-up of 18·9 months (IQR 10·4-23·8), progression-free survival as assessed by the study investigator was significantly prolonged with atezolizumab versus control (15·1 vs 10·6 months; hazard ratio [HR] 0·78; 95% CI 0·63-0·97; p=0·025). Common treatment-related adverse events (>30%) in the atezolizumab and control groups were blood creatinine phosphokinase increased (51·3% vs 44·8%), diarrhoea (42·2% vs 46·6%), rash (40·9%, both groups), arthralgia (39·1% vs 28·1%), pyrexia (38·7% vs 26·0%), alanine aminotransferase increased (33·9% vs 22·8%), and lipase increased (32·2% vs 27·4%); 13% of patients in the atezolizumab group and 16% in the control group stopped all treatment because of adverse events.
INTERPRETATION
The addition of atezolizumab to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and significantly increased progression-free survival in patients with BRAF
FUNDING
F Hoffmann-La Roche and Genentech.
Identifiants
pubmed: 32534646
pii: S0140-6736(20)30934-X
doi: 10.1016/S0140-6736(20)30934-X
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Azetidines
0
Piperidines
0
Vemurafenib
207SMY3FQT
atezolizumab
52CMI0WC3Y
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
cobimetinib
ER29L26N1X
Banques de données
ClinicalTrials.gov
['NCT02908672']
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
1835-1844Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.