Biweekly Cetuximab Plus FOLFOX6 as First-Line Therapy in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The CEBIFOX Trial.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Cetuximab
/ administration & dosage
Colorectal Neoplasms
/ drug therapy
Drug Administration Schedule
Exons
/ genetics
Female
Fluorouracil
/ administration & dosage
Humans
Leucovorin
/ administration & dosage
Male
Middle Aged
Organoplatinum Compounds
/ administration & dosage
Progression-Free Survival
Proto-Oncogene Proteins p21(ras)
/ genetics
Young Adult
BRAF mutation
Biweekly cetuximab
Metastatic colorectal cancer
Primary tumor localization
RAS mutation
Journal
Clinical colorectal cancer
ISSN: 1938-0674
Titre abrégé: Clin Colorectal Cancer
Pays: United States
ID NLM: 101120693
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
11
06
2019
revised:
27
02
2020
accepted:
11
03
2020
pubmed:
2
8
2020
medline:
23
11
2021
entrez:
2
8
2020
Statut:
ppublish
Résumé
The multicenter, single-arm, phase II study CEBIFOX evaluated the efficacy of a biweekly cetuximab administration in combination with FOLFOX6 as first-line therapy in KRAS (exon 2) wild-type (wt) metastatic colorectal cancer (mCRC). Patients received FOLFOX6 with cetuximab (500 mg/m In total, 57 were included in the intention-to-treat (ITT) analyses. New RAS mutations were detected in 14.0% by post hoc next-generation sequencing analysis in 43 patients. The ORR in the all RASwt population was 70.3% with a median PFS and OS of 10.9 (95% confidence interval [CI], 9.0-12.9) and 33.8 (95% CI, 21.1-45.5) months. Grade 3-5 adverse events occurred in 66.7% of the ITT, without significant impact on the PRO. Patients with right-sided primary tumors had a reduced ORR (54.5%), and median PFS and OS (10.1 and 23.8 months). BRAF mutations were detected in 11.3%. These patients had a significantly lower ORR, and median PFS and OS. Patients with RASwt/BRAFwt tumors had a notably high median PFS and OS of 14.3 and 38.9 months. This study supports the efficacy and safety of biweekly cetuximab given in combination with FOLFOX6 in patients with RASwt/BRAFwt mCRC with left-sided primary tumor. CEBIFOX is the first trial reporting the complete dataset, including extended molecular profiling and tumor location of a biweekly administered cetuximab/FOLFOX6 in mCRC. Clinical trial number: NCT01051167.
Sections du résumé
BACKGROUND
The multicenter, single-arm, phase II study CEBIFOX evaluated the efficacy of a biweekly cetuximab administration in combination with FOLFOX6 as first-line therapy in KRAS (exon 2) wild-type (wt) metastatic colorectal cancer (mCRC).
PATIENTS AND METHODS
Patients received FOLFOX6 with cetuximab (500 mg/m
RESULTS
In total, 57 were included in the intention-to-treat (ITT) analyses. New RAS mutations were detected in 14.0% by post hoc next-generation sequencing analysis in 43 patients. The ORR in the all RASwt population was 70.3% with a median PFS and OS of 10.9 (95% confidence interval [CI], 9.0-12.9) and 33.8 (95% CI, 21.1-45.5) months. Grade 3-5 adverse events occurred in 66.7% of the ITT, without significant impact on the PRO. Patients with right-sided primary tumors had a reduced ORR (54.5%), and median PFS and OS (10.1 and 23.8 months). BRAF mutations were detected in 11.3%. These patients had a significantly lower ORR, and median PFS and OS. Patients with RASwt/BRAFwt tumors had a notably high median PFS and OS of 14.3 and 38.9 months.
CONCLUSIONS
This study supports the efficacy and safety of biweekly cetuximab given in combination with FOLFOX6 in patients with RASwt/BRAFwt mCRC with left-sided primary tumor. CEBIFOX is the first trial reporting the complete dataset, including extended molecular profiling and tumor location of a biweekly administered cetuximab/FOLFOX6 in mCRC. Clinical trial number: NCT01051167.
Identifiants
pubmed: 32737003
pii: S1533-0028(20)30040-2
doi: 10.1016/j.clcc.2020.03.003
pii:
doi:
Substances chimiques
KRAS protein, human
0
Organoplatinum Compounds
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Cetuximab
PQX0D8J21J
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Banques de données
ClinicalTrials.gov
['NCT01051167']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
236-247.e6Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.