Comprehensive genomic profiling by liquid biopsy captures tumor heterogeneity and identifies cancer vulnerabilities in patients with RAS/BRAF

anti-epidermal growth factor receptor (EGFR) drugs circulating tumor DNA (ctDNA) colorectal cancer (CRC) comprehensive genomic profiling (CGP) liquid biopsy

Journal

Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735

Informations de publication

Date de publication:
28 Aug 2024
Historique:
received: 28 06 2024
revised: 14 08 2024
accepted: 15 08 2024
medline: 31 8 2024
pubmed: 31 8 2024
entrez: 30 8 2024
Statut: aheadofprint

Résumé

Emerging evidence supports tumor tissue-based comprehensive genomic profiling (CGP) in metastatic colorectal cancer (mCRC). Data on liquid biopsy-based circulating tumor DNA (ctDNA) CGP are scarce and mainly retrospective. Prospective comparison between the two tests is not currently available. The CAPRI 2-GOIM trial investigates efficacy and safety of ctDNA-driven, cetuximab-based, sequence of three treatment lines in patients with RAS/BRAF For 2/207 (0.96%) patients, no ctDNA was detected by F1L CDx. No patient displayed tumor fraction (TF) below 1%, whereas elevated ctDNA (TF≥10%) was detected among 140/205 (68.3%) patients. 1013 genomic variants were identified. F1L CDx found KRAS, NRAS or BRAF Baseline liquid biopsy-based CGP is feasible, it has high concordance with tumor tissue-based CGP, it could better recapitulate tumor heterogeneity, and it is clinically informative by identifying additional actionable genomic alterations in approximately half of RAS/BRAF

Sections du résumé

BACKGROUND BACKGROUND
Emerging evidence supports tumor tissue-based comprehensive genomic profiling (CGP) in metastatic colorectal cancer (mCRC). Data on liquid biopsy-based circulating tumor DNA (ctDNA) CGP are scarce and mainly retrospective. Prospective comparison between the two tests is not currently available.
METHODS METHODS
The CAPRI 2-GOIM trial investigates efficacy and safety of ctDNA-driven, cetuximab-based, sequence of three treatment lines in patients with RAS/BRAF
RESULTS RESULTS
For 2/207 (0.96%) patients, no ctDNA was detected by F1L CDx. No patient displayed tumor fraction (TF) below 1%, whereas elevated ctDNA (TF≥10%) was detected among 140/205 (68.3%) patients. 1013 genomic variants were identified. F1L CDx found KRAS, NRAS or BRAF
CONCLUSION CONCLUSIONS
Baseline liquid biopsy-based CGP is feasible, it has high concordance with tumor tissue-based CGP, it could better recapitulate tumor heterogeneity, and it is clinically informative by identifying additional actionable genomic alterations in approximately half of RAS/BRAF

Identifiants

pubmed: 39214459
pii: S0923-7534(24)03914-0
doi: 10.1016/j.annonc.2024.08.2334
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Investigateurs

Davide Ciardiello (D)
Luca Boscolo Bielo (LB)
Stefania Napolitano (S)
Erika Martinelli (E)
Teresa Troiani (T)
Antonella Nicastro (A)
Tiziana Pia Latiano (TP)
Paola Parente (P)
Evaristo Maiello (E)
Antonio Avallone (A)
Nicola Normanno (N)
Salvatore Pisconti (S)
Claudia Nisi (C)
Roberto Bordonaro (R)
Alessia Erika Russo (AE)
Emiliano Tamburrini (E)
Ilaria Toma (I)
Claudio Lotesoriere (C)
Simona Vallarelli (S)
Maria Giulia Zampino (MG)
Nicola Fazio (N)
Giuseppe Curigliano (G)
Fortunato Ciardiello (F)
Giulia Martini (G)
Sara Lonardi (S)
Chiara Cremolini (C)
Carlo Garufi (C)
Pierosandro Tagliaferri (P)
Giampaolo Tortora (G)
Filippo Pietrantonio (F)
Antonio Febbraro (A)
Gerardo Rosati (G)
Silvana Leo (S)
Oronzo Brunetti (O)
Rosanna Berardi (R)
Saverio Cinieri (S)
Mario Scartozzi (M)
Alberto Zaniboni (A)
Giancarlo Paoletti (G)

Informations de copyright

Copyright © 2024 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.

Auteurs

D Ciardiello (D)

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy.

L B Bielo (LB)

Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.

S Napolitano (S)

Department of Precision Medicine, The University of Campania Luigi Vanvitelli, Naples, Italy.

E Martinelli (E)

Department of Precision Medicine, The University of Campania Luigi Vanvitelli, Naples, Italy.

T Troiani (T)

Department of Precision Medicine, The University of Campania Luigi Vanvitelli, Naples, Italy.

A Nicastro (A)

Department of Precision Medicine, The University of Campania Luigi Vanvitelli, Naples, Italy.

T P Latiano (TP)

Medical Oncology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

P Parente (P)

Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

E Maiello (E)

Medical Oncology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

A Avallone (A)

Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.

N Normanno (N)

IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Mendola, Italy.

S Pisconti (S)

Medical Oncology Unit, San Giuseppe Moscati Hospital, Statte, Italy.

C Nisi (C)

Medical Oncology Unit, San Giuseppe Moscati Hospital, Statte, Italy.

R Bordonaro (R)

Medical Oncology Unit, Azienda Ospedaliera ARNAS Garibaldi, Catania, Italy.

A E Russo (AE)

Medical Oncology Unit, Azienda Ospedaliera ARNAS Garibaldi, Catania, Italy.

E Tamburrini (E)

Department of Oncology and Palliative Care, Cardinale G Panico, Tricase City Hospital, Tricase, Italy.

I Toma (I)

Department of Oncology and Palliative Care, Cardinale G Panico, Tricase City Hospital, Tricase, Italy.

C Lotesoriere (C)

Medical Oncology Unit, National Institute of Gastroenterology, IRCCS de Bellis Research Hospital, Castellana Grotte, Italy.

S Vallarelli (S)

Medical Oncology Unit, National Institute of Gastroenterology, IRCCS de Bellis Research Hospital, Castellana Grotte, Italy.

M G Zampino (MG)

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy.

N Fazio (N)

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy.

G Curigliano (G)

Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.

F De Vita (F)

Department of Precision Medicine, The University of Campania Luigi Vanvitelli, Naples, Italy.

F Ciardiello (F)

Department of Precision Medicine, The University of Campania Luigi Vanvitelli, Naples, Italy. Electronic address: fortunato.ciardiello@unicampania.it.

G Martini (G)

Department of Precision Medicine, The University of Campania Luigi Vanvitelli, Naples, Italy.

Classifications MeSH