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Br J Cancer. 2017 May 9;116(10):1271-1278. doi: 10.1038/bjc.2017.93. Epub 2017 Apr 11.

Cetuximab in treatment of metastatic colorectal cancer: final survival analyses and extended RAS data from the NORDIC-VII study.

Author information

1
Department of Oncology, Oslo University Hospital, Oslo, Norway.
2
K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway.
3
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
4
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
5
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
6
Department of Clinical Science, University of Bergen, Bergen, Norway.
7
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
8
Department of Oncology, Odense University Hospital, Odense, Denmark.
9
Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
10
Department of Oncology, Tampere University Hospital, Tampere, Finland.
11
Department of Oncology, Landspitali, Reykjavik, Iceland.
12
Department of Pathology, Oslo University Hospital, Oslo, Norway.
13
Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
14
Department of Pharmacology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

Abstract

BACKGROUND:

The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis.

METHODS:

A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study. Updated survival status was obtained from 176 patients who were alive in the primary survival analyses. Samples from 223 tumours previously found to be KRAS (exon 2) and BRAF (V600E) wild-type, were re-analysed for KRAS (exons 3 and 4) and NRAS (exons 2-4) mutations.

RESULTS:

Including the extended RAS analyses, RAS and BRAF mutational status was available from 457 patients (81% of the ITT population). RAS was mutated in 46% and BRAF in 12% of the tumours. RAS and BRAF, if mutated, were negative prognostic factors. The updated analyses confirmed the finding of the primary report that cetuximab did not provide any additional benefit when added to FLOX in patients with RAS/BRAF wild-type tumours, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy.

CONCLUSIONS:

Adding cetuximab to Nordic FLOX did not provide any clinical benefit, but the data suggested an effect of cetuximab monotherapy in patients with RAS/BRAF wild-type tumours in the NORDIC-VII cohort. The data were compatible with a negative interaction between cetuximab and the Nordic FLOX chemotherapy backbone.

PMID:
28399112
PMCID:
PMC5482736
DOI:
10.1038/bjc.2017.93
[Indexed for MEDLINE]
Free PMC Article

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