AUTHOR=Martini Giulia , Ciardiello Davide , Napolitano Stefania , Martinelli Erika , Troiani Teresa , Latiano Tiziana Pia , Avallone Antonio , Normanno Nicola , Di Maio Massimo , Maiello Evaristo , Ciardiello Fortunato 

TITLE=Efficacy and safety of a biomarker-driven cetuximab-based treatment regimen over 3 treatment lines in mCRC patients with RAS/BRAF wild type tumors at start of first line: The CAPRI 2 GOIM trial

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1069370

DOI=10.3389/fonc.2023.1069370

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Monoclonal antibodies targeting EGFR such as cetuximab or panitumumab represent a major step forward in the treatment of <italic>RAS</italic> wild type (WT) metastatic colorectal cancer (mCRC). Unfortunately, primary and acquired resistance mechanisms occur, with a huge percentage of patients succumbing to the disease. In the last years, <italic>RAS</italic> mutation has been identified as the main molecular driver that determine resistance to anti-EGFR monoclonal antibodies. Liquid biopsy analysis allows to a dynamic and longitudinal assessment of mutational status during mCRC disease and has provided important information on the use of anti-EGFR drugs beyond progression or as rechallenge strategy in patients with <italic>RAS</italic> WT tumors.</p></sec><sec><title>Methods</title><p>The phase II CAPRI 2 GOIM trial investigates the efficacy and safety of a bio-marker-driven cetuximab-based treatment regimen over 3 treatment lines in mCRC patients with <italic>RAS/BRAF</italic> WT tumors at start of first line.</p></sec><sec><title>Discussion</title><p>The aim of the study is to identify patients with <italic>RAS/BRAF</italic> WT tumors defined as “addicted” to an-anti EGFR based treatment along three lines of therapy. Moreover, the trial will evaluate the activity of cetuximab re-introduction in combination with irinotecan as 3<sup>rd</sup> line therapy as rechallenge for patients that will be treated in second line with FOLFOX plus bevacizumab, having a <italic>RAS/BRAF</italic> mutant disease at progression after FOLFIRI plus cetuximab first line. A novel characteristic of this program is that the therapeutic algorithm will be defined at each treatment decision (<italic>first line, second line and third line</italic>) in a prospective fashion in each patient by a liquid biopsy assessment of <italic>RAS/BRAF</italic> status by a comprehensive 324 genes Foundation One Liquid assay (Foundation/Roche).</p></sec><sec><title>Trial registration</title><p>EudraCT Number: 2020-003008-15, <uri xlink:href="https://ClinicalTrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</uri> identifier: NCT05312398.</p></sec>