Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Nov:157:71-80.
doi: 10.1016/j.ejca.2021.08.017. Epub 2021 Sep 8.

Consensus molecular subtypes in metastatic colorectal cancer treated with sequential versus combined fluoropyrimidine, bevacizumab and irinotecan (XELAVIRI trial)

Arndt Stahler  1 , Volker Heinemann  2 , Veronika Schuster  3 , Kathrin Heinrich  3 , Annika Kurreck  4 , Clemens Gießen-Jung  3 , Ludwig Fischer von Weikersthal  5 , Florian Kaiser  6 , Thomas Decker  7 , Swantje Held  8 , Ullrich Graeven  9 , Ingo Schwaner  10 , Claudio Denzlinger  11 , Michael Schenk  12 , Jens Neumann  13 , Thomas Kirchner  14 , Andreas Jung  14 , Jörg Kumbrink  14 , Sebastian Stintzing  15 , Dominik P Modest  15
Affiliations
Clinical Trial

Consensus molecular subtypes in metastatic colorectal cancer treated with sequential versus combined fluoropyrimidine, bevacizumab and irinotecan (XELAVIRI trial)

Arndt Stahler et al. Eur J Cancer. 2021 Nov.

Abstract

Background: The XELAVIRI trial compared sequential (fluoropyrimidine and bevacizumab; irinotecan (Iri) at progression) versus initial combination therapy (fluoropyrimidine, bevacizumab, Iri) of treatment-naïve metastatic colorectal cancer (mCRC). In the confirmatory analysis, the primary end-point (non-inferiority of sequential therapy regarding time to failure of strategy, TFS) was not met. Nevertheless, significant differences regarding treatment efficacy were observed according to RAS status. Here, we evaluate the consensus molecular subtypes (CMS) as additional biomarkers for sequential versus combination therapy.

Material and methods: Gene expression was measured using NanoString after mRNA extraction from formalin-fixed paraffin-embedded tumour specimens. CMS were predicted using multinomial regression and correlated with updated data for TFS, overall (OS) and progression-free survival.

Results: CMS were predicted in 337 of 421 (80.0%) patients (CMS1: 18.4%; CMS2: 51.6%; CMS3: 2.7%; CMS4: 27.3%). CMS2 together with RAS/BRAF wild-type status was identified as potential predictive marker of benefit from initial combination therapy for OS (HR 0.56, 95% CI 0.33-0.96, p = 0.036) and progression-free survival (HR 0.28, 95% CI 0.29-0.79, p = 0.004) and also trending in TFS (HR 0.63, 90% CI 0.41-0.95, p = 0.066). In patients with RAS-mutated mCRC, CMS1 was associated with longer OS after initial combination therapy (HR 0.43, 95% CI 0.20-0.95, p = 0.038). Interaction testing (two-sided) of CMS and RAS/BRAF status in favour of the combination treatment strategy was significant for OS (p = 0.012) CONCLUSIONS: In patients with RAS/BRAF wild-type mCRC, CMS2 may serve as an additional biomarker of benefit from the initial combination therapy, including Iri.

Trial registration: Trial registration ID (clinicaltrials.gov) NCT01249638.

Keywords: Bevacizumab; Consensus molecular subtypes; Metastatic colorectal cancer; RAS; Sequential.

PubMed Disclaimer

Publication types

Associated data