dc.contributor
Institut Català de la Salut
dc.contributor
[Randon G] Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Nakamura Y] Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan. [Yaeger R] Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. [Lonardi S] Department of Oncology, Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy. [Cremolini C] Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. [Elez E, Ros J] Medical Oncology Department, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Randon, Giovanni
dc.contributor.author
Nakamura, Yoshiaki
dc.contributor.author
CREMOLINI, CHIARA
dc.contributor.author
Yaeger, Rona
dc.contributor.author
Lonardi, Sara
dc.contributor.author
Elez, Elena
dc.contributor.author
Ros, Javier
dc.date.accessioned
2025-10-25T05:39:33Z
dc.date.available
2025-10-25T05:39:33Z
dc.date.issued
2024-02-14T09:20:40Z
dc.date.issued
2024-02-14T09:20:40Z
dc.date.issued
2024-01-15
dc.identifier
Randon G, Nakamura Y, Yaeger R, Lonardi S, Cremolini C, Elez E, et al. Negative Hyperselection of Patients with HER2+ and RAS Wild-Type Metastatic Colorectal Cancer Receiving Dual HER2 Blockade: the PRESSING-HER2 Study. Clin Cancer Res. 2024 Jan 15;30(2):436–43.
dc.identifier
https://hdl.handle.net/11351/11044
dc.identifier
10.1158/1078-0432.CCR-23-1379
dc.identifier.uri
http://hdl.handle.net/11351/11044
dc.description.abstract
Hyperselection; Metastatic colorectal cancer
dc.description.abstract
Hiperselección; Cáncer colorrectal metastásico
dc.description.abstract
Hiperselecció; Càncer colorectal metastàtic
dc.description.abstract
Purpose:
To demonstrate the negative prognostic impact of a panel of genomic alterations (PRESSING-HER2 panel) and lack of HER2 amplification by next-generation sequencing (NGS) in patients with HER2+, RAS wild-type metastatic colorectal cancer receiving dual HER2 blockade.
Experimental Design:
The PRESSING-HER2 panel of HER2 mutations/rearrangements and RTK/MAPK mutations/amplifications was assessed by NGS. HER2 amplification was confirmed by NGS if copy-number variation (CNV) was ≥ 6. With a case–control design, hypothesizing 30% and 5% PRESSING-HER2 positivity in resistant [progression-free survival (PFS) <4 months and no RECIST response] versus sensitive cohorts, respectively, 35 patients were needed per group.
Results:
PRESSING-HER2 alterations included HER2 mutations/rearrangements, EGFR amplification, and BRAF mutations and had a prevalence of 27% (9/33) and 3% (1/35) in resistant versus sensitive patients (P = 0.005) and 63% predictive accuracy. Overall, HER2 nonamplified status by NGS had 10% prevalence. Median PFS and overall survival (OS) were worse in PRESSING-HER2+ versus negative (2.2 vs. 5.3 months, P < 0.001; 5.4 vs. 14.9 months, P = 0.001) and in HER2 nonamplified versus amplified (1.6 vs. 5.2 months, P < 0.001; 7.4 vs. 12.4 months, P = 0.157). These results were confirmed in multivariable analyses [PRESSING-HER2 positivity: PFS HR = 3.06, 95% confidence interval (CI), 1.40–6.69, P = 0.005; OS HR = 2.93, 95% CI, 1.32–6.48, P = 0.007]. Combining PRESSING-HER2 and HER2 CNV increased the predictive accuracy to 75%.
Conclusions:
PRESSING-HER2 panel and HER2 nonamplified status by NGS warrant validation as potential predictive markers in this setting.
dc.description.abstract
This study was supported by AIRC IG 23624 (to F. Pietrantonio), and by the NIH Cancer Center Core Grant P30 CA008748 to Memorial Sloan Kettering Cancer Center.
dc.format
application/pdf
dc.publisher
American Association for Cancer Research
dc.relation
Clinical Cancer Research;30(2)
dc.relation
https://doi.org/10.1158/1078-0432.CCR-23-1379
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Medicaments antineoplàstics - Ús terapèutic
dc.subject
Anomalies cromosòmiques
dc.subject
Còlon - Càncer - Tractament
dc.subject
Recte - Càncer - Tractament
dc.subject
DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
dc.subject
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
dc.title
Negative Hyperselection of Patients with HER2+ and RAS Wild-Type Metastatic Colorectal Cancer Receiving Dual HER2 Blockade: the PRESSING-HER2 Study
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
