Circulating tumor DNA driving anti-EGFR rechallenge therapy in metastatic colorectal cancer: the RASINTRO prospective multicenter study
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: In RAS wild-type (WT) metastatic colorectal cancer (mCRC), preliminary data have suggested that circulating tumor DNA (ctDNA) may select patients for anti-EGFR rechallenge therapy. METHODS: RASINTRO is a prospective nonrandomized study evaluating anti-EGFR rechallenge strategy in third and later line treatment in RAS/BRAF WT mCRC. Liquid biopsies for ctDNA analysis were collected before the first (C1) and second (C2) cycles of anti-EGFR rechallenge therapy. The primary endpoint was the progression-free survival (PFS) according to RAS/BRAF mutational status on ctDNA at C1. RESULTS: Among 74 patients screened between November 2017 and March 2020, 62 were enrolled: median age, 66.1 years; median number of previous lines of therapy, 3; panitumumab or cetuximab rechallenge alone (66.2%) or with chemotherapy (33.8%); ctDNA RAS/BRAF status at C1, 42 WT (67.7%) and 20 mutated (32.3%). Median PFS (3.3 vs 1.9 months: hazard ratio (HR) = 0.43; P <.01) and overall survival (OS) (7.9 vs 4.9 months; HR = 0.46; P =.01) were significantly longer for patients with ctDNA RAS/BRAF WT vs mutated at C1. Among the 32 patients with ctDNA RAS/BRAF WT at C1 and available blood samples at C2, those who have experienced an early decrease of >50% in ctDNA concentration (n = 15) had a significantly longer median PFS (4.2 vs 2.8 months; HR = 0.39; P =.01) and OS (10.2 vs 4.2 months; HR = 0.39; P =.02). CONCLUSION: This study showed that anti-EGFR rechallenge therapy in refractory disease is more effective in patients with RAS/BRAF WT on ctDNA, and in those who experienced an early decrease of >50% in ctDNA concentration. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03259009.
DOI: 10.1093/jnci/djaf229
Authors: Aziz Zaanan, Elisabeth Sophie Bergen, Ludovic Evesque, Aurelia Meurisse, Pascal Artru, Thierry Lecomte, Olivier Bouché, Céline Lepère, Margherita Ambrosini, Romain Coriat, Astrid Lièvre, Romain Cohen, Valérie Boige, Samy Louafi, Jean-Baptiste Bachet, Sophie Goyer, Julien Taieb, Dewi Vernerey, Hélène Blons, Pierre Laurent-Puig
Institutions: Inserm, Université Paris Cité, Sorbonne Université, Centre de Recherche des Cordeliers, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Medical University of Vienna, Centre Antoine Lacassagne, Centre Hospitalier Universitaire de Besançon, Methodology and Quality of Life Unit in Oncology, Interactions Hôte-Greffon-Tumeur & Ingénierie Cellulaire et Génique, Université de Franche-Comté, Hôpital Privé Jean Mermo, Université de Tours, Centre Hospitalier Universitaire de Tours, Niche, Nutrition, Cancer et métabolisme oxydatif, Centre Hospitalier Universitaire de Reims, Université de Reims Champagne-Ardenne, Hôpital Cochin, Oncogenesis Stress Signaling, Hôpital Pontchaillou, Université Rennes 1, Université de Rennes, La Ligue Contre le Cancer, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Institut Gustave Roussy, Fondation Gustave Roussy, Centre Hospitalier Sud Francilien, Pitié-Salpêtrière Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Amgen, AstraZeneca
OpenAlex ID: W4413346165