Randomised trial of trastuzumab deruxtecan and biology-driven selection of neoadjuvant treatment for HER2-positive breast cancer : a study protocol of ARIADNE
| Title: | Randomised trial of trastuzumab deruxtecan and biology-driven selection of neoadjuvant treatment for HER2-positive breast cancer : a study protocol of ARIADNE |
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| Authors: | Matikas, Alexios; Naume, Bjorn; Wildiers, Hans; Sonke, Gabe; Dieci, Maria Vittoria; Karakatsanis, Andreas; Andersson, Anne; Barnekow, Elin; Kessler, Luisa Edman; Einbeigi, Zakaria; Killander, Fredrika; Linderholm, Barbro; Schiza, Aglaia; Valachis, Antonis; Nearchou, Andreas; Engebraaten, Olav; Porojnicu, Alina; Hiorth Soland, Mari; Mannsåker, Bård; Raj, Sunil X.; Store Blix, Egil; Soma Nordstrand, Cecilie; Lambertini, Matteo; Vernieri, Claudio; Punie, Kevin; Sotiriou, Christos; Bergh, Jonas; Villacampa, Guillermo; Zouzos, Athanasios; Hellström, Mats; Hartman, Johan; Foukakis, Theodoros |
| Publisher Information: | Uppsala universitet, Endokrinkirurgi; Uppsala universitet, Science for Life Laboratory, SciLifeLab; Uppsala universitet, Cancerimmunterapi; Breast Center, Theme Cancer, Karolinska University Hospital and Karolinska Comprehensive Cancer Center, Stockholm, Sweden; Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Oncology, Oslo University Hospital, Oslo, Norway; Department of General Medical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium; Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, Università di Padova, Padova, Italy; Oncologia 2, Istituto Oncologico Veneto IRCCS, Padova, Italy; Department of diagnostics and intervention, oncology, Umeå University, Umeå, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Department of Oncology, Södersjukhuset, Stockholm, Sweden; Breast Center, Capio Saint Göran’s Hospital, Stockholm, Sweden; Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Medicine and Oncology, Southern Älvsborg Hospital, Borås, Sweden; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Faculty of Medicine, Skåne University Hospital, Lund University, Lund, Sweden; Institution of Clinical Sciences, Department of Oncology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden; Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Oncology, Mälarsjukhuset, Eskilstuna, Sweden; Department of Oncology, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway; Department of Oncology, Stavanger University Hospital, Stavanger, Norway; Department of Oncology, Nordland Hospital Trust, Bodø, Norway; Breast Cancer Unit, Cancer Clinic, University Hospital in Trondheim, Trondheim, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway; Department of Oncology, Møre og Romsdal Hospital Trust, Alesund, Norway; Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy; Medical Oncology Department, Breast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; Oncology and Hematology-Oncology Department, University of Milan, Milan, Italy; Department of Medical Oncology, Ziekenhuis Aan de Stroom, Wilrijk, Belgium; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium; SOLTI Cancer Research Group, Barcelona, Spain; Statistics Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital and Karolinska Comprehensive Cancer Center, Stockholm, Sweden; Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden |
| Publication Year: | 2025 |
| Collection: | Uppsala University: Publications (DiVA) |
| Subject Terms: | Breast tumours; Clinical trials; Drug Therapy; Cancer and Oncology; Cancer och onkologi |
| Description: | Introduction: Neoadjuvant therapy is the standard of care for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). Studies on first-generation antibody-drug conjugates, such as trastuzumab emtansine (T-DM1), showed equal or slightly lower efficacy than chemotherapy combined with dual HER2 blockade. Trastuzumab deruxtecan (T-DXd) is a next-generation conjugate approved for the treatment of metastatic HER2-positive and HER2-low BC, with greatly improved efficacy compared to T-DM1. Methods and analysis: ARIADNE is an academic, international, open-label, randomised, comparative phase IIB trial. A total of 370 patients with non-metastatic HER2-positive BC and an indication for neoadjuvant therapy will be included and randomised 1:1 to receive either (1) docetaxel (or paclitaxel), carboplatin, trastuzumab (H) and pertuzumab (P) for three cycles or (2) T-DXd for three cycles. Further treatment is based on the intrinsic molecular subtype determined by the Prosigna assay: patients with HER2-enriched disease (estimated 60%) continue the same treatment for three more cycles. Patients with oestrogen receptor (ER)-positive and luminal (estimated 30%) disease receive H and P for three cycles, combined with letrozole and ribociclib for two cycles. Patients with ER-negative and luminal, basal-like or normal-like disease (estimated 10%) either continue the same treatment for three more cycles in the case of a radiologic complete response, or, in the case of no complete response, they receive four cycles of dose-dense epirubicin and cyclophosphamide. The primary endpoint of ARIADNE is locally assessed rate of pathologic complete response in the molecularly HER2-enriched population, defined as ypT0/Tis, ypN0, as determined by a pathologist blinded to treatment assignment (intention-to-treat (ITT) analysis). Key secondary endpoints include time-to-event endpoints (event-free, recurrence-free, distant recurrence-free and overall survival), safety, health-related quality of life and ... |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | English |
| Relation: | BMJ Open, 2025, 15:8; PMID 40866060; ISI:001561459600001 |
| DOI: | 10.1136/bmjopen-2025-102626 |
| Availability: | http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-567705; https://doi.org/10.1136/bmjopen-2025-102626 |
| Rights: | info:eu-repo/semantics/openAccess |
| Accession Number: | edsbas.7781D523 |
| Database: | BASE |