Taieb, J;
Balogoun, R;
Le Malicot, K;
Tabernero, J;
Mini, E;
Folprecht, G;
Van Laethem, JL;
... PETACC8 investigators, .; + view all
(2016)
Adjuvant FOLFOX +/- cetuximab in full RAS and BRAF wildtype stage III colon cancer patients.
Annals of Oncology
10.1093/annonc/mdw687.
(In press).
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Abstract
BACKGROUND: RAS mutations have been shown to confer resistance to anti-EGFR treatment. We analyzed the results of the PETACC8 trial (cetuximab + FOLFOX vs FOLFOX) in full RAS and BRAF wildtype (WT) patients (pts) with resected stage III colon cancer. METHODS: Exons 2, 3 and 4 of KRAS and NRAS, and BRAF exons 11 and 15, were sequenced using the Ampliseq colon-lung cancer panel version 2, in PETACC8 trial pts who consented to translational research. The impact of cetuximab on time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS) was investigated in pts with tumors harboring RAS & BRAF WT and RAS mutations. The prognostic value of each individual mutation was also tested. RESULTS: Among the 2559 pts analyzed, 745 pts (29%) were known to have KRAS exon 2 mutations and 163 pts (6.4%) the BRAF V600E mutation. Of the remaining 1651 pts, 1054 were assessed by NGS, showing that a further 227 pts (21%) had KRAS exon 2,3,4 or NRAS exon 2,3,4 mutations, and that 46 pts (4.4%) had a newly diagnosed BRAF mutation. Cetuximab added to FOLFOX did not significantly improve TTR, DFS or OS in pts with RAS WT or RAS & BRAF WT tumors (HR 0.77 to 1.03, all P>0.05). Cetuximab addition was not either significantly deleterious in RAS mutant pts or in pts with rare RAS or BRAF mutations. In the overall trial population, NRAS and KRAS codon 61 mutations were the only rare mutations with the same pejorative prognostic value as KRAS exon 2 or BRAF V600E mutations. CONCLUSION: Though not significant, the clinically relevant 0.76 adjusted HR observed for DFS in favor of adding cetuximab to FOLFOX, in full RAS and BRAF WT stage III colon cancer pts, may justify a new randomized controlled trial testing EGFR inhibitors in this setting.Clinical trial number: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23.
| Type: | Article |
|---|---|
| Title: | Adjuvant FOLFOX +/- cetuximab in full RAS and BRAF wildtype stage III colon cancer patients |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/annonc/mdw687 |
| Publisher version: | https://doi.org/10.1093/annonc/mdw687 |
| Language: | English |
| Additional information: | Copyright © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. This is a pre-copyedited, author-produced version of an article accepted for publication in Annals of Oncology following peer review. The version of record [FULL CITATION] is available online at: https://doi.org/10.1093/annonc/mdw687 |
| Keywords: | BRAF mutations, FOLFOX, RAS mutations, adjuvant, cetuximab, phase III, prognosis, stage III colon cancer |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1534421 |
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