Integrating tissue and liquid biopsy comprehensive genomic profiling to predict efficacy of anti-EGFR therapies in metastatic colorectal cancer: Findings from the CAPRI-2 GOIM study
- PMID: 40669385
- DOI: 10.1016/j.ejca.2025.115642
Integrating tissue and liquid biopsy comprehensive genomic profiling to predict efficacy of anti-EGFR therapies in metastatic colorectal cancer: Findings from the CAPRI-2 GOIM study
Abstract
Introduction: We investigated the role of integrating tissue biopsy (TBx)- and liquid biopsy (LBx)-comprehensive genomic profiling (CGP) to predict the activity of FOLFIRI plus cetuximab.
Methods: The CAPRI-2 GOIM study is a non-randomized phase 2 study evaluating a biomarker-driven anti-EGFR treatment in three lines of therapy in patients with RAS/BRAFV600E wild type metastatic colorectal cancer. At baseline, TBx and LBx were analyzed using the FoundationOne CDx platform. Analysis of overall response rate (ORR) and median progression free survival (mPFS) according to molecular profiles were performed.
Results: Overall, 156 patients were evaluable for tumor response and had matched tissue and plasma-based CGP. Negatively hyper-selected patients by both TBx- and LBx-CGP showed higher ORR (79.6 % versus 44.2 %, P < 0.001) and mPFS compared to mutated cases (12.4 months versus 7.4 months, P < 0.001). Eight and 12 cases harbored mutations detected by TBx and LBx-CGP only, respectively. Compared to discordant cases (n = 20), concordant cases (n = 23) showed a trend for lower ORR (39.1 % versus 50.0 %, P = 0.5) and shorter mPFS (3.94 versus 11.50 months, P = 0.02). Patients with alterations detected only by TBx-CGP had significantly lower circulating tumor DNA (ctDNA) tumor fraction (TF) compared to concordant cases (1.7 % versus 23.0 %; P = 0.01). Using a ctDNA TF threshold ≥ 10 % nearly all (19 of 20) TBx detected pathogenic variants (PV) were also identified by LBx-CGP. In eight cases detected by LBx only, mPFS was 8.24 months.
Conclusion: In cases with high TF LBx-CGP predicts efficacy of anti-EGFR therapy, while for TF< 10 % TBx-CGP provides additional data on PVs that could affect treatment efficacy.
Keywords: Anti-EGFR drugs; Cetuximab; Comprehensive genomic profiling; Liquid biopsy; Metastatic colorectal cancer; NGS.
Copyright © 2025 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Davide Ciardiello: reported receiving travel support from Merck KGaA, Sanofi, and BMS; advisory board Bayer outside the submitted work. Stefania Napolitano: reported receiving personal fees from Novartis and a travel grant from Amgen outside the submitted work. Roberto Bordonaro: reported receiving honoraria: Novartis, AstraZeneca, Sanofi, Amgen, Roche, Pfizer, Janssen-Cilag, and Bristol Myers Squibb; consulting or advisory role: Novartis, Bayer, AstraZeneca, Sanofi, Amgen, Roche, Pfizer, Janssen-Cilag, and Bristol Myers Squibb; speakers’ bureau: AstraZeneca, Sanofi, Novartis, Bayer, Amgen, Roche, Pfizer, Janssen-Cilag, and Bristol Myers Squibb. Sara Lonardi: reported Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, Lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi Sankyo, Bristol Myers Squibb, Astellas, GSK, Takeda, Bayer; Financial Interests, Personal, Invited Speaker: Pierre Fabre, GSK, Roche, Servier, Amgen, Bristol Myers Squibb, Incyte, Lilly, Merck Serono, MSD; Financial Interests, Institutional, Invited Speaker: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, Bristol Myers Squibb; Non-Financial Interests, Member of Board of Directors, Italian No-Profit Oncology Research Foundation supporting academic Clinical trials: GONO. Chiara Cremolini: reported receiving grants and personal fees from Merck and Amgen outside the submitted work. Giampaolo Tortora: reported consulting or advisory role for per Bristol Myers Squibb, Astra-Zeneca, Merck, Merck Sharp & Dohme, SERVIER. Filippo Pietrantonio: reported receiving Research funding (to Institution) from Lilly, BMS, Incyte, AstraZeneca, Amgen, Agenus, Rottapharm. Personal honoraria as an invited speaker from BeiGene, Daiichi-Sankyo, Seagen, Astellas, Ipsen, AstraZeneca, Servier, Bayer, Takeda, Johnson & Johnson, BMS, MSD, Amgen, Merck-Serono, Pierre-Fabre. Advisory/Consultancy from BMS, MSD, Amgen, Pierre-Fabre, Johnson & Johnson, Servier, Bayer, Takeda, Astellas, GSK, Daiichi-Sankyo, Pfizer, BeiGene, Jazz Pharmaceuticals, Incyte, Rottapharm, Merck-Serono, Italfarmaco, Gilead, AstraZeneca, Agenus. Antonio Lucenti: reported receiving honoraria for Servier, Astra Zeneca, Amgen outside the submitted work. Rossana Berardi: reported consultant/advisory board member for Astra Zeneca, Boehringer Ingelheim, Novartis, MSD, Otsuka, Eli-Lilly, Roche outside the submitted work. Erika Martinelli: reported serving as advisor and speaker for AstraZeneca, Eli Lilly, Servier, Sanofi Genzyme, Roche, Merck, Eisai, and Pfizer outside the submitted work. Teresa Troiani: received travel grants from AstraZeneca and Pierre Fabre and is an advisory board member for AstraZeneca, Bayer, Amgen, Merck, Roche, Sanofi, Servier, and Pierre Fabre. Nicola Normanno: reported receiving honoraria: Thermo Fisher Scientific, Lilly, MSD, Illumina, Merck Serono, Incyte, Biocartis, AstraZeneca, and MSD; consulting or advisory role: Biocartis, AstraZeneca, Bayer, Incyte, Novartis, and Roche; research funding: AstraZeneca (Inst), Biocartis (Inst), Illumina (Inst), Incyte (Inst), Merck Serono (Inst), Qiagen (Inst), Roche (Inst), and Thermo Fisher Scientific (Inst); travel, accommodations, expenses: Merck Serono. Paola Parente: served as speaker/pathologist consultant for Amgen, Pierre Fabre, MSD, Servier, BeiGene, Astra Zeneca, Bristol, Incyte, Pharmacogenetics, Daiichi-Sankyio, Astellas, GSK outside the submitted work. Nicola Fazio: reported receiving research funds from and serving on an advisory board for Merck outside the submitted work. Giuseppe Curigliano: reported receiving honoraria for speaker’s engagement: Roche, Seattle Genetics, Novartis, Lilly, Pfizer, Foundation Medicine, NanoString, Samsung, Celltrion, BMS, and MSD; honoraria for providing consultancy: Roche, Seattle Genetics, and NanoString; honoraria for participating in advisory board: Roche, Lilly, Pfizer, Foundation Medicine, Samsung, Celltrion, and Mylan; honoraria for writing engagement: Novartis and BMS; honoraria for participation in Ellipsis Scientific Affairs Group; institutional research funding for conducting phase I and II clinical trials: Pfizer, Roche, Novartis, Sanofi, Celgene, Servier, Orion, AstraZeneca, Seattle Genetics, AbbVie, Tesaro, BMS, Merck Serono, Merck Sharp Dohme, Janssen-Cilag, Philogen, Bayer, Medivation, and Medimmune. Antonio Avallone: reported receiving personal fees from Amgen, AstraZeneca, Merck, Sharp & Dohme, Eisai, and Bristol Myers Squibb outside the submitted work. Evaristo Maiello: reported serving as advisor and speaker for AstraZeneca, Eli Lilly, Servier, Sanofi Genzyme, Roche, Merck, Eisai, and Pfizer outside the submitted work. Fortunato Ciardiello: received institutional research grants from Amgen, Merck KGaA, Merck Sharp & Dohme, Pfizer, Pierre Fabre, Roche, and Servier; and service on advisory boards for Bayer, Merck KGaA, Merck Sharp & Dohme, Pierre Fabre, Roche, and Servier outside the submitted work. Giulia Martini: reported receiving honoraria from Servier, Incyte, and Pierre Fabre outside the submitted work. All other authors have declared no conflicts of interest.
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