TY - JOUR
T1 - Long-term Survival Update and Extended RAS Mutational Analysis of the CAIRO2 Trial
T2 - Addition of Cetuximab to CAPOX/Bevacizumab in Metastatic Colorectal Cancer
AU - ten Hoorn, Sanne
AU - Mol, Linda
AU - Sommeijer, Dirkje W.
AU - Nijman, Lisanne
AU - van den Bosch, Tom
AU - de Back, Tim R.
AU - Ylstra, Bauke
AU - van Dijk, Erik
AU - van Noesel, Carel J. M.
AU - Reinten, Roy J.
AU - Nagtegaal, Iris D.
AU - Koopman, Miriam
AU - Punt, Cornelis J. A.
AU - Vermeulen, Louis
N1 - Funding Information: We thank Dirk H.F.B. van Essen for performing the Whole Exome Sequencing experiments. Louis Vermeulen received consultancy fees/research funding from Bayer, MSD, Genentech, Servier and Pierre Fabre, but these had no relation to the presented work. The rest of the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This work was supported by the Dutch Cancer Society (KWF) and the New York Stem Cell Foundation (NYSCF). Publisher Copyright: © 2022 The Author(s)
PY - 2022
Y1 - 2022
N2 - Background: Here we present updated survival of the CAIRO2 trial and assessed whether the addition of anti-EGFR to anti-VEGF therapy could still be an effective treatment option for patients with extended RAS/BRAF wildtype and left-sided metastatic colorectal cancer (mCRC). Materials and Methods: Retrospective updated survival and extended RAS and BRAF V600E mutational analysis were performed in the CAIRO2 trial, a multicenter, randomized phase III trial on the effect of adding cetuximab to a combination of capecitabine, oxaliplatin (CAPOX), and bevacizumab in mCRC. Results: Updated survival analysis confirmed that the addition of cetuximab did not provide a benefit on either progression free (PFS) or overall survival (OS) in the intention-to-treat population. With the extended mutational analyses 31 KRAS, 31 NRAS and 12 BRAF V600E additional mutations were found. No benefit of the addition of cetuximab was observed within the extended wildtype group, even when selecting only left-sided tumors (PFS HR 0.96, p = 0.7775). However, compared to the original trial an increase of 6.5 months was seen for patients with both extended wildtype and left-sided tumors (median OS 28.6 months). Conclusion: Adding cetuximab to CAPOX and bevacizumab does not provide clinical benefit in patients with mCRC, even in the extended wildtype group with left-sided tumors. However, in the extended wildtype group we did observe clinically relevant higher survival compared to the initial trial report, indicating that it is important to analyze a broader panel of RAS and BRAF variants using more recent sequencing techniques when assessing survival benefit after anti-EGFR therapy.
AB - Background: Here we present updated survival of the CAIRO2 trial and assessed whether the addition of anti-EGFR to anti-VEGF therapy could still be an effective treatment option for patients with extended RAS/BRAF wildtype and left-sided metastatic colorectal cancer (mCRC). Materials and Methods: Retrospective updated survival and extended RAS and BRAF V600E mutational analysis were performed in the CAIRO2 trial, a multicenter, randomized phase III trial on the effect of adding cetuximab to a combination of capecitabine, oxaliplatin (CAPOX), and bevacizumab in mCRC. Results: Updated survival analysis confirmed that the addition of cetuximab did not provide a benefit on either progression free (PFS) or overall survival (OS) in the intention-to-treat population. With the extended mutational analyses 31 KRAS, 31 NRAS and 12 BRAF V600E additional mutations were found. No benefit of the addition of cetuximab was observed within the extended wildtype group, even when selecting only left-sided tumors (PFS HR 0.96, p = 0.7775). However, compared to the original trial an increase of 6.5 months was seen for patients with both extended wildtype and left-sided tumors (median OS 28.6 months). Conclusion: Adding cetuximab to CAPOX and bevacizumab does not provide clinical benefit in patients with mCRC, even in the extended wildtype group with left-sided tumors. However, in the extended wildtype group we did observe clinically relevant higher survival compared to the initial trial report, indicating that it is important to analyze a broader panel of RAS and BRAF variants using more recent sequencing techniques when assessing survival benefit after anti-EGFR therapy.
KW - Gastrointestinal cancer, Adjuvant chemotherapy, Anti-EGFR, Anti-VEGF
KW - Molecular subtypes
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85144806227&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36564280
UR - http://www.scopus.com/inward/record.url?scp=85144806227&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.clcc.2022.11.006
DO - https://doi.org/10.1016/j.clcc.2022.11.006
M3 - Article
C2 - 36564280
SN - 1533-0028
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
ER -