Sistema de Salut de Catalunya
Institut Català de la Salut
[Yaeger R] Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. [Martini JF] Translational Science Operations, Pfizer, Inc., La Jolla, California. [Pasquina L] Clinical Development, Foundation Medicine Inc., Boston, Massachusetts. [Tunquist B] Formerly Pfizer, Inc., New York, New York. [Zhang X] Global Development, Pfizer, Inc., South San Francisco, California. [Kaiser F] Formerly Foundation Medicine Inc., Boston, Massachusetts. [Tabernero J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. University of Vic – Central University of Catalonia, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-10-29T08:06:43Z
2025-10-29T08:06:43Z
2025-09
BRAF inhibitor; Colorectal cancer
Inhibidor de BRAF; Cáncer colorrectal
Inhibidor de BRAF; Càncer colorectal
Purpose: The BRAF inhibitor encorafenib (Enco) plus the anti-EGFR antibody cetuximab (Cetux) improved overall survival, objective response rate, and progression-free survival in previously treated BRAFV600E-mutant metastatic colorectal cancer in BEACON, a phase III randomized trial, leading to regulatory approval for this indication. To support rapid, plasma-based testing for BRAFV600E identification, clinical validity of a ctDNA-based assay, FoundationOneLiquid CDx (F1LCDx), was assessed against the reference tumor-based clinical trial assay (CTA) in liquid biopsy-evaluable samples from BEACON and commercially obtained tissue-matched plasma samples. Patients and methods: Pretreatment 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 BRAFV600E was found between F1LCDx and CTA, with a positive percent agreement of 87.2% and negative percent agreement of 97.1%. Among 42 F1LCDx-/CTA+ samples, 41 (97.6%) had ctDNA tumor fraction <1%. Among samples with ctDNA tumor fraction >1%, the positive percent agreement was 99.4% and negative percent agreement was 86.7%. Clinical outcomes with Enco plus Cetux 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 BRAFV600E alterations in patients with metastatic colorectal cancer, particularly when ctDNA tumor fraction was >1%. Significance: In the phase III BEACON trial, which established Enco plus Cetux as a standard of care for previously treated BRAFV600E-mutant metastatic colorectal cancer, mutational status was confirmed through testing of tumor tissue. To support rapid, less invasive testing for BRAFV600E in plasma, this retrospective study assessed a ctDNA-based assay and found strong concordance between the liquid biopsy test and the tumor-based assay in detecting BRAFV600E.
Article
Published version
English
Anomalies cromosòmiques; Còlon - Càncer - Tractament; Recte - Càncer - Tractament; Marcadors tumorals; Quimioteràpia combinada; DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation; CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación; COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada
American Association for Cancer Research
Cancer Research Communications;5(9)
https://doi.org/10.1158/2767-9764.CRC-25-0002
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3393]
