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

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

doi:10.3389/fonc.2023.1069370

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

Front Oncol. 2023 Feb 13:13:1069370. doi: 10.3389/fonc.2023.1069370. eCollection 2023.

Affiliations

¹ Dipartimento di Medicina di Precisione, Oncologia Medica, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy.
² Oncologia Medica, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
³ Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Oncologia Clinica Sperimentale Addome, Napoli, Italy.
⁴ Biologia Cellulare e Bioterapie, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"-Istituto di Ricovero e Cura a Carattere Scientifico, Napoli, Italy.
⁵ Dipartimento di Oncologia, Università di Torino, Azienda Ospedaliera Mauriziana, Torino, Italy.

Abstract

Background: Monoclonal antibodies targeting EGFR such as cetuximab or panitumumab represent a major step forward in the treatment of RAS 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, RAS 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 RAS WT tumors.

Methods: 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 RAS/BRAF WT tumors at start of first line.

Discussion: The aim of the study is to identify patients with RAS/BRAF 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^rd line therapy as rechallenge for patients that will be treated in second line with FOLFOX plus bevacizumab, having a RAS/BRAF 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 (first line, second line and third line) in a prospective fashion in each patient by a liquid biopsy assessment of RAS/BRAF status by a comprehensive 324 genes Foundation One Liquid assay (Foundation/Roche).

Trial registration: EudraCT Number: 2020-003008-15, ClinicalTrials.gov identifier: NCT05312398.

Keywords: EGFR; biomarker; cetuximab; colorectal cancer; liquid biopsy.

Associated data

ClinicalTrials.gov/NCT05312398

Grants and funding

All the costs for the study implementation will be in charge of the sponsor Gruppo Oncologico dell’Italia Meridionale (GOIM), that will receive from Merck Serono S.p.A. a partial economical support and the study Investigational Medicinal Product (IMP) provision.