Sistema de Salut de Catalunya
Institut Català de la Salut
[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
Vall d'Hebron Barcelona Hospital Campus
2024-02-14T09:20:40Z
2024-02-14T09:20:40Z
2024-01-15
Hyperselection; Metastatic colorectal cancer
Hiperselección; Cáncer colorrectal metastásico
Hiperselecció; Càncer colorectal metastàtic
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.
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.
Article
Published version
English
Medicaments antineoplàstics - Ús terapèutic; Anomalies cromosòmiques; Còlon - Càncer - Tractament; Recte - Càncer - Tractament; DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
American Association for Cancer Research
Clinical Cancer Research;30(2)
https://doi.org/10.1158/1078-0432.CCR-23-1379
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
