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Peer-reviewedCC BY-NC-ND 4.0Supportive Care in Cancer

Managing trastuzumab deruxtecan-related adverse events in patients with metastatic breast cancer: insights from a worldwide survey of the Hermione EDUcational project

9 more authors
32 affiliations
  1. 1Phase 1 Research Centre, Fondazione IRCCS San Gerardo Dei Tintori, Monza, MB Italy
  2. 2School of Medicine and Surgery, University of Milano-Bicocca, Monza, MB Italy
  3. 3Genolier Cancer Center, Clinique de Genolier, Genolier, Switzerland
  4. 4Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
  5. 5Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Madrid, Spain
  6. 6Department of Nursing, Cyprus University of Technology, Limassol, Cyprus
  7. 7Medical Oncology, Azienda USL-IRCCS Reggio Emilia, Reggio Emilia, Italy
  8. 8Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy
  9. 9Medical Oncology Department, Unidade Local de Saúde Santa Maria, Lisbon, Portugal
  10. 10Gulbenkian Institute for Molecular Medicine, Lisbon, Portugal
  11. 11Faculty of Medicine, University of Lisbon, Lisbon, Portugal
  12. 12University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Department of Gynecology and Obstetrics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
  13. 13Translational Genomics and Targeted Therapies in Solid Tumors, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
  14. 14Department of Radiation Oncology, Hospital Clinic de Barcelona, Barcelona, Spain
  15. 15Department of Medical Oncology, Lyon University Hospital, HCL, Lyon, France
  16. 16Université de Lyon, Lyon, France
  17. 17Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
  18. 18Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194 Japan
  19. 19Cancer Center, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194 Japan
  20. 20Bartholomew’s Hospital, London, UK
  21. 21National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
  22. 22City of Hope, Atlanta, GA USA
  23. 23Department of Medicine, Division of Hematology Oncology, University of California San Diego, San Diego, CA USA
  24. 24Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  25. 25Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA USA
  26. 26Advanced Cancer Translational Research Institute, Showa Medical University, Tokyo, Japan
  27. 27Hoch Health Ostschweiz St. Gallen, St. Gallen, Switzerland
  28. 28University of Bern, Bern, Switzerland
  29. 29Cancer Fatigue Clinic (Schaffhausen, Münsterlingen, Sargans), St. Gallen, Switzerland
  30. 30Facultat de Medicina I Ciencias de La Salut, Universitat de Barcelona (UB), Barcelona, Spain
  31. 31Department of Hematology Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile
  32. 32Sun Yat-Sen University, Guangzhou, China

Abstract

Purpose: Trastuzumab deruxtecan (T-DXd) has shown remarkable efficacy in phase III trials in patients with HER2-positive early- and late-stage breast cancer and HER2-low/ultra-low metastatic breast cancer (mBC). However, toxicities remain prevalent and clinically relevant, leading to dose reductions/interruptions or discontinuation.

Methods: A survey was conducted across oncologists in 13 countries worldwide to collect experiences in managing T-DXd-related toxicities, focusing on nausea/vomiting, fatigue, and interstitial lung disease (ILD) as key areas of clinical concern.

Results: Ninety-nine experts participated in the survey. Nausea and fatigue were the most common toxicities, reported by 91.9% and 94.9% of respondents, respectively. 5-HT3 receptor antagonists, NK1 receptor antagonists, and corticosteroids were “very often” prescribed for prophylaxis. The frequency of use of second‑generation 5‑HT3 receptor antagonists varied among respondents. Most frequently, they employed an NK1 receptor antagonist combined with corticosteroids and 5‑HT3 receptor antagonists. Forty-four percent of respondents prescribed 4‑drug regimens incorporating NK1 receptor antagonists and olanzapine to all patients with nausea/vomiting above grade 1 in the first cycle, 35% reserved them for high‑risk patients, and 21% used them for all patients from cycle one. For all respondents, patients receiving T‑DXd experienced fatigue, with 65% observing it in more than 60% of patients, and most considered nausea/vomiting and fatigue to moderately or significantly affect daily activities and quality of life. ILD was reported as rare or occasional and was generally monitored using computed tomography.

Conclusion: Real-life management of T-DXd-related toxicities is complex and needs an ongoing comprehensive evaluation of patients before, during and after therapy, with a highly trained/skilled multidisciplinary team.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00520-026-11393-4.

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BibTeX
@article{cazzaniga2026managing,
  title = {{Managing trastuzumab deruxtecan-related adverse events in patients with metastatic breast cancer: insights from a worldwide survey of the Hermione EDUcational project}},
  author = {Marina Elena Cazzaniga and Matti Aapro and Manuel Alva Bianchi and Andreas Charalambous and Laura Cortesi and Luis Costa and Peter Fashing and Ana Belen Rodriguez Garcia and Freyer Gilles and Bryan Hennessy and Hirotoshi Iihara and Maria Lapuente and Fei Ma and Irati Rodriguez Matesanz and Kelly Elizabeth McCann and Yeon Hee Park and Hope S. Rugo and Hitomi Sakai and Florian Strasser and Benjamin Walbaum and Shusen Wang},
  journal = {Supportive Care in Cancer},
  year = {2026},
  month = oct,
  doi = {10.1007/s00520-026-11393-4},
  url = {https://doi.org/10.1007/s00520-026-11393-4},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Managing trastuzumab deruxtecan-related adverse events in patients with metastatic breast cancer: insights from a worldwide survey of the Hermione EDUcational project
AU  - Marina Elena Cazzaniga
AU  - Matti Aapro
AU  - Manuel Alva Bianchi
AU  - Andreas Charalambous
AU  - Laura Cortesi
AU  - Luis Costa
AU  - Peter Fashing
AU  - Ana Belen Rodriguez Garcia
AU  - Freyer Gilles
AU  - Bryan Hennessy
AU  - Hirotoshi Iihara
AU  - Maria Lapuente
AU  - Fei Ma
AU  - Irati Rodriguez Matesanz
AU  - Kelly Elizabeth McCann
AU  - Yeon Hee Park
AU  - Hope S. Rugo
AU  - Hitomi Sakai
AU  - Florian Strasser
AU  - Benjamin Walbaum
AU  - Shusen Wang
PY  - 2026
DA  - 2026/10/31
JO  - Supportive Care in Cancer
DO  - 10.1007/s00520-026-11393-4
UR  - https://doi.org/10.1007/s00520-026-11393-4
AB  - Purpose: Trastuzumab deruxtecan (T-DXd) has shown remarkable efficacy in phase III trials in patients with HER2-positive early- and late-stage breast cancer and HER2-low/ultra-low metastatic breast cancer (mBC). However, toxicities remain prevalent and clinically relevant, leading to dose reductions/interruptions or discontinuation.  Methods: A survey was conducted across oncologists in 13 countries worldwide to collect experiences in managing T-DXd-related toxicities, focusing on nausea/vomiting, fatigue, and interstitial lung disease (ILD) as key areas of clinical concern.  Results: Ninety-nine experts participated in the survey. Nausea and fatigue were the most common toxicities, reported by 91.9% and 94.9% of respondents, respectively. 5-HT3 receptor antagonists, NK1 receptor antagonists, and corticosteroids were “very often” prescribed for prophylaxis. The frequency of use of second‑generation 5‑HT3 receptor antagonists varied among respondents. Most frequently, they employed an NK1 receptor antagonist combined with corticosteroids and 5‑HT3 receptor antagonists. Forty-four percent of respondents prescribed 4‑drug regimens incorporating NK1 receptor antagonists and olanzapine to all patients with nausea/vomiting above grade 1 in the first cycle, 35% reserved them for high‑risk patients, and 21% used them for all patients from cycle one. For all respondents, patients receiving T‑DXd experienced fatigue, with 65% observing it in more than 60% of patients, and most considered nausea/vomiting and fatigue to moderately or significantly affect daily activities and quality of life. ILD was reported as rare or occasional and was generally monitored using computed tomography.  Conclusion: Real-life management of T-DXd-related toxicities is complex and needs an ongoing comprehensive evaluation of patients before, during and after therapy, with a highly trained/skilled multidisciplinary team.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00520-026-11393-4.
SN  - 0941-4355
SN  - 1433-7339
ER  -