Faculty, Staff and Student Publications

Publication Date

8-20-2025

Journal

Cancer Research Communications

DOI

10.1158/2767-9764.CRC-25-0002

PMID

40832988

Abstract

Background: The BRAF inhibitor encorafenib plus the anti-EGFR antibody cetuximab improved overall survival, objective response rate, and progression-free survival in previously treated BRAF V600E-mutant metastatic colorectal cancer in BEACON, a phase 3 randomized trial, leading to regulatory approval for this indication. To support rapid, plasma-based testing for BRAF V600E identification, clinical validity of a circulating tumor DNA (ctDNA)-based assay, FoundationOne®Liquid CDx (F1LCDx) was assessed, versus the reference tumor-based clinical trial assay (CTA) in liquid biopsy-evaluable samples from BEACON and commercially-obtained tissue-matched plasma samples.

Methods: Pre-treatment tissue samples were collected in BEACON to confirm BRAF mutational status using the central single gene PCR assay. Concordance between the CTA and liquid biopsy tests was assessed, and clinical validity of liquid biopsy testing was examined using clinical outcomes from BEACON.

Results: Of the 523 evaluable patients, 433 with matched tissue and plasma samples had CTA and F1LCDx results available (BEACON, n=328; commercial, n=105). A strong concordance in detecting BRAF V600E was found between F1LCDx and CTA, with a positive percent agreement (PPA) of 87.2% and negative percent agreement (NPA) of 97.1%. Among 42 F1LCDx-/CTA+ samples, 41 (97.6%) had ctDNA tumor fraction < 1%. Among samples with ctDNA tumor fraction >1%, the PPA was 99.4% and NPA was 86.7%. Clinical outcomes with encorafenib plus cetuximab were similar between those identified as F1LCDx+/CTA+ and CTA+ overall.

Conclusions: This study supports using liquid biopsies as a clinically valid assay for identifying BRAF V600E alterations in patients with mCRC, particularly when ctDNA tumor fraction was >1%.

Published Open-Access

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