Effectiveness of first-line cetuximab in wild-type RAS metastatic colorectal cancer according to tumour BRAF mutation status from the EREBUS cohort.
anticancer drugs
cancer
genotyping
pharmacoepidemiology
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
06
02
2020
revised:
15
06
2020
accepted:
26
06
2020
pubmed:
14
7
2020
medline:
27
7
2021
entrez:
14
7
2020
Statut:
ppublish
Résumé
Poor efficacy has been reported for patients with BRAF mutations for metastatic colorectal cancer (mCRC). EREBUS is a French cohort study of wild-type (wt) KRAS unresectable mCRC patients initiating a first-line treatment with cetuximab from 2009 to 2010, followed for two years (five years for vital status). Molecular genetics platforms have provided additional RAS and BRAF mutation testing results. Progression-free survival (PFS) and overall survival (OS) were assessed according to tumour mutation (mt) status: RASmt/BRAFany, RASwt/BRAFmt and RASwt/BRAFwt. Multivariate Cox analyses were used to evaluate association between mutation status and death or progression. A total of 389 patients were included in 65 centres and with a known tumour mutation status: 64 RASmt/BRAFany (21%), 33 RASwt/BRAFmt (13%) and 213 RASwt/BRAFwt (87%). Respective baseline characteristics were: median age 65, 64 and 63 years, male gender 63%, 64% and 69%, Eastern Cooperative Oncology Group performance status ≤ 1 75%, 76% and 79%, and liver-only metastases 39%, 33% and 40%. Median progression-free survival was 8.0 months [5.9-9.3] for patients with RASmt/BRAFany, 6.0 months [2.3-7.2] for patients with RASwt/BRAFmt, and 10.4 months [9.5-11.0] for patients with RASwt/BRAFwt. Respectively, median overall survival was 18.4 months [10.9-23.3], 9.7 months [6.9-16.6] and 29.3 months [26.3-36.1]. In multivariate analyses, progression (HR = 2.71 [1.79-4.10]) and death (HR = 2.79 [1.81-4.30]) were more likely for RASwt/BRAFmt vs RASwt/BRAFwt patients. BRAF mutations were associated with markedly poorer outcomes in initially unresectable RASwt mCRC patients treated by cetuximab in first-line treatment.
Substances chimiques
KRAS protein, human
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Cetuximab
PQX0D8J21J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1120-1128Subventions
Organisme : Merck Serono S.A.S., an affiliate of Merck KGaA, Darmstadt, Germany
Informations de copyright
© 2020 The British Pharmacological Society.
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