Analytical and clinical validation of PATHWAY HER2 (4B5) assay for assessment of HER2-low/HER2-ultralow status and eligibility for trastuzumab deruxtecan in DESTINY-Breast06
Rattachement africain : sg, au, us, it, cn, fr, jp, be, ch, pl, es. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
BACKGROUND: The DESTINY-Breast06 study demonstrated a statistically significant and clinically meaningful improvement in progression-free survival benefit with trastuzumab deruxtecan (T-DXd) versus chemotherapy treatment of physician's choice in patients with hormone receptor-positive metastatic breast cancer (mBC) whose tumors were scored as human epidermal growth factor receptor 2 (HER2)-low [immunohistochemistry (IHC) 1+, or IHC 2+/in situ hybridization (ISH)-negative] and who had received one or more lines of endocrine therapy and no previous chemotherapy in the metastatic setting. An exploratory analysis consistently showed a benefit for patients with HER2-low and HER2-ultralow (IHC 0 with membrane staining) expression. MATERIALS AND METHODS: Analytical validation of the PATHWAY HER2 (4B5) assay (Roche HER2 4B5 assay; Roche Diagnostic Solutions) at the HER2-ultralow cut-off was carried out, including intermediate precision, inter-reader precision, and inter-laboratory reproducibility. Patients with tumors historically classified as HER2-negative (IHC 0, 1+, and 2+/ISH-negative) based on pre-existing local test results were eligible for screening for DESTINY-Breast06; tumor samples taken in the metastatic setting were assessed centrally to confirm eligibility regarding HER2 status. Additionally, central and pre-existing HER2 test results were compared, and the prevalence of IHC scores based on central test results was assessed. RESULTS: Intermediate precision met the pre-specified endpoints across all parameters tested; agreement was observed within and between readers and sites, demonstrating that the HER2-ultralow cut-off can be scored accurately and reproducibly using the Roche HER2 4B5 assay (intra- and inter-laboratory and inter-reader agreement ≥95%). A clinically meaningful progression-free survival (hazard ratios 0.43-0.78) and objective response rate (odds ratios 2.5-4.5) improvement for T-DXd over chemotherapy was consistently observed across IHC expression levels. For cases with a pre-existing HER2 IHC 0 result, central testing found 24% with HER2-low, 40% with IHC 0 with membrane staining, and 35% with IHC 0 absent membrane staining. CONCLUSIONS: For patients with HER2 IHC 0 mBC, rescoring and/or retesting with the Roche HER2 4B5 assay is encouraged to determine eligibility for T-DXd.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Analytical and clinical validation of PATHWAY HER2 (4B5) assay for assessment of HER2-low/HER2-ultralow status and eligibility for trastuzumab deruxtecan in DESTINY-Breast06
- Date Crossref
- 01/06/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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AstraZeneca (Singapore) pays non établi dans la noticeEntreprise
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Peter MacCallum Cancer Centre pays non établi dans la noticeÉtablissement de santé
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University of California Division of Hematology/Oncology pays non établi dans la noticeUniversité ou école supérieure
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European Institute of Oncology pays non établi dans la noticeÉtablissement de santé
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Fudan University Department of Medical Oncology pays non établi dans la noticeUniversité ou école supérieure
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National Cancer Centre Singapore pays non établi dans la noticeÉtablissement de santé
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Université Paris Cité Department of Medical Oncology pays non établi dans la noticeUniversité ou école supérieure
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Institut Curie pays non établi dans la noticeOrganisation à but non lucratif
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SHOWA Medical University Hospital The Innovative Center of Translational Research and Clinical Science for Cancer Therapy pays non établi dans la noticeÉtablissement de santé
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KU Leuven pays non établi dans la noticeUniversité ou école supérieure
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Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte pays non établi dans la noticeÉtablissement de santé
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Candiolo Cancer Institute pays non établi dans la noticeOrganisation à but non lucratif
AstraZeneca (Singapore), Peter MacCallum Cancer Centre et Division of Hematology/Oncology — University of California, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.