Circulating tumor DNA driving anti-EGFR rechallenge therapy in metastatic colorectal cancer: the RASINTRO prospective multicenter study.

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

Published in

Journal of the National Cancer Institute. Aug 20, 2025. Epub Aug 20, 2025.

Abstract

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.
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) cycle of anti-EGFR rechallenge therapy. The primary endpoint was the progression-free survival (PFS) according to RAS/BRAF mutational status on ctDNA at C1.
Among 74 patients screened between November 2017 to 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: HR = 0.43; P < .01) and 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 more than 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).
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 more 50% in ctDNA concentration. (NCT03259009).

PMID:
40833930
Bibliographic data and abstract were imported from PubMed on 21 Aug 2025.

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