Vemurafenib in non-small-cell lung cancer patients with BRAF
BRAF
basket trial
biomarker
lung cancer
personalised therapy
vemurafenib
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
17
06
2019
revised:
08
10
2019
accepted:
20
10
2019
entrez:
22
1
2020
pubmed:
22
1
2020
medline:
7
1
2021
Statut:
ppublish
Résumé
BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). Of the 118 patients enrolled, 101 presented with a BRAF Routine biomarker screening of NSCLC should include BRAF ClinicalTrials.gov identifier: NCT02304809.
Sections du résumé
BACKGROUND
BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort.
PATIENTS AND METHODS
Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS).
RESULTS
Of the 118 patients enrolled, 101 presented with a BRAF
CONCLUSION
Routine biomarker screening of NSCLC should include BRAF
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT02304809.
Identifiants
pubmed: 31959346
pii: S0923-7534(19)36079-X
doi: 10.1016/j.annonc.2019.10.022
pii:
doi:
Substances chimiques
Vemurafenib
207SMY3FQT
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Banques de données
ClinicalTrials.gov
['NCT02304809']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
289-294Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.