2022
DOI: 10.1158/1078-0432.ccr-22-1696
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Liquid Biopsy Detects Early Molecular Response and Predicts Benefit to First-Line Chemotherapy plus Cetuximab in Metastatic Colorectal Cancer: PLATFORM-B Study

Abstract: Purpose: Chemotherapy plus anti-EGFR is standard first-line therapy in RAS wt metastatic colorectal cancer (mCRC) but biomarkers of early response are clinically needed. We aimed to define the utility of ctDNA to assess early response in mCRC patients receiving first-line anti-EGFR therapy. Experimental Design: Prospective multicentric study of tissue RAS wt mCRC patients treated with first-line chemotherapy plus cetuximab undergoing sequential liquid biopsies. Baseline and early (C3) ctDNA were analyzed by NG… Show more

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Cited by 19 publications
(11 citation statements)
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“…Since 2022, three studies regarding anti-EGFR agents induced acquired alternations of ctDNA in patients treated in first-line were published [ 48 50 ]. They demonstrated that lower prevalence of acquired genomic alternations by first-line anti-EGFR therapy (6.6–9%), of which is similar to our present findings.…”
Section: Discussionmentioning
confidence: 99%
“…Since 2022, three studies regarding anti-EGFR agents induced acquired alternations of ctDNA in patients treated in first-line were published [ 48 50 ]. They demonstrated that lower prevalence of acquired genomic alternations by first-line anti-EGFR therapy (6.6–9%), of which is similar to our present findings.…”
Section: Discussionmentioning
confidence: 99%
“…However, upon metastatic spread and after several lines of drug pressure, heterogeneity becomes greater, and heterogeneity is underrepresented by a single tumor re-biopsy ( Gerlinger et al, 2012 ; Amirouchene-Angelozzi et al, 2017 ; Dang et al, 2020 ). A different approach to study tumoral molecular heterogeneity is the use of (serial) liquid biopsies, which are able to detect the genomic landscape shed into the bloodstream by the different subclones (spatial heterogeneity), in a minimally-invasive blood extraction which can be repeated as many times as necessary to track the evolving sub-clonal genetic abnormalities (temporal heterogeneity) ( Van Emburgh et al, 2016 ; Amirouchene-Angelozzi et al, 2017 ; Dasari et al, 2020 ; Vidal et al, 2022 ).…”
Section: Acquired Resistance To Anti-egfr Moab In Mcrc: Heterogeneity...mentioning
confidence: 99%
“…Moreover, the ease-of-use and minimally-invasive procedure allow serial assessment of the genomic landscape to closely track emerging subclones of resistance. In mCRC, several cohort studies and retrospective analysis from clinical trials have shown the utility of liquid biopsy to monitor the genomic landscape and track the emergence of resistant clones in patients treated with anti-EGFR therapies ( Diaz Jr et al, 2012 ; Misale et al, 2012 ; Siravegna et al, 2015a ; Montagut et al, 2018 ; Vitiello et al, 2019 ; Dasari et al, 2020 ; Vidal et al, 2022 ).…”
Section: Liquid Biopsy To Monitor Clonal Dynamics and Track Mechanism...mentioning
confidence: 99%
“…Early assessment of tumor response is crucial to guide treatment decisions towards improved patient outcomes. Overall, several studies demonstrated that a decrease of ctDNA can predict tumor response to chemotherapy and anti-EGFR therapy as soon as 2 weeks after treatment administration in mCRC, usually remarkably anticipating response by conventional imaging and CEA standard biomarker ( 31, 44–46 ). Besides anti-EGFR agents and chemotherapy, the predictive value of ctDNA dynamic was also confirmed for other targeted strategies, such as anti-HER2, anti-BRAF/EGFR, and KRAS G12C -directed regimens ( 36, 40, 47 ).…”
Section: Longitudinal Ctdna Monitoring To Detect and Trade Off Acquir...mentioning
confidence: 99%