American Association for Cancer Research
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FigureS1 from Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study)

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posted on 2023-03-31, 20:30 authored by Fanny Garlan, Pierre Laurent-Puig, David Sefrioui, Nathalie Siauve, Audrey Didelot, Nasrin Sarafan-Vasseur, Pierre Michel, Geraldine Perkins, Claire Mulot, Hélène Blons, Julien Taieb, Frederic Di Fiore, Valerie Taly, Aziz Zaanan

Supplementary Figure 1. Impact of baseline ctDNA concentration on overall survival (OS) in the subgroup of patients included before the 1st line of treatment (n=68).

Funding

Ministère de l'Enseignement Supérieur et de la Recherche

Université Paris Descartes

CNRS

INSERM

INCA

ARC

ANR

FdV

History

ARTICLE ABSTRACT

Purpose: Markers of chemotherapy efficacy in metastatic colorectal cancer (mCRC) are essential for optimization of treatment strategies. We evaluated the applicability of early changes in circulating tumor DNA (ctDNA) as a marker of therapeutic efficacy.Experimental Design: This prospective study enrolled consecutive patients with mCRC receiving a first- or second-line chemotherapy. CtDNA was assessed in plasma collected before the first (C0), second (C1) and/or third (C2) chemotherapy cycle, using picodroplet-digital PCR assays based either on detection of gene mutation (KRAS, BRAF, TP53) or hypermethylation (WIF1, NPY). CT scans were centrally assessed using RECIST v1.1 criteria. Multivariate analyses were adjusted on age, gender, ECOG performance status (PS), metastatic synchronicity, and treatment line.Results: Eighty-two patients with mCRC treated in first- (82.9%) or second- (17.1%) line chemotherapy were included. Patients with a high (>10 ng/mL) versus low (≤0.1 ng/mL) ctDNA concentration at C0 had a shorter overall survival (OS; 6.8 vs. 33.4 months: adjusted HR, 5.64; 95% CI, 2.5–12.6; P < 0.0001). By analyzing the evolution of the ctDNA concentration between C0 and C2 or C1 (C2or1), we classified the patients in two groups (named “good” or “bad ctDNA responders”). In multivariate analysis, patients belonging to the group called “good ctDNA responder” (n = 58) versus “bad ctDNA responder” (n = 15) had a better objective response rate (P < 0.001), and a longer median progression-free survival (8.5 vs. 2.4 months: HR, 0.19; 95% CI, 0.09–0.40; P < 0.0001) and OS (27.1 vs. 11.2 months: HR, 0.25; 95% CI, 0.11–0.57; P < 0.001).Conclusions: This study suggests that early change in ctDNA concentration is a marker of therapeutic efficacy in patients with mCRC. Clin Cancer Res; 23(18); 5416–25. ©2017 AACR.