A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05)
Summary
Patients with HER2-positive primary breast cancer (BC) who do not achieve complete response after appropriate neoadjuvant therapy are at higher risk of disease recurrence. More effective treatment options are needed for this patient population. This study will examine the efficacy and safety of trastuzumab deruxtecan (T-DXd) compared with trastuzumab emtansine (T-DM1) in high-risk patients with residual invasive breast cancer following neoadjuvant therapy.
Timeline
- Start
- 2020-12-04
- Primary completion
- 2025-07-02
- Completion
- 2028-06-20
Outcome
Met primary endpoint
paper postneoadjuvant T-DXd resulted in a significantly higher likelihood of invasive disease-free survival than T-DM1 PMID 41370739 ↗
release “DESTINY-Breast05 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a highly statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS)” astrazeneca.com ↗
release “Based on DESTINY-Breast05 Phase III trial results which showed Enhertu reduced the risk of invasive disease recurrence or death by 53% compared with T-DM1” astrazeneca.com ↗
release “In DESTINY-Breast05, Enhertu as an adjuvant treatment reduced the risk of invasive disease recurrence or death (invasive disease-free survival [IDFS]) by 53%” astrazeneca.com ↗
Publications
- Loibl S, Park YH, Shao Z, Huang CS, Barrios C, Abraham J, Prat A, Niikura N, Im SA, Li W, Li H, Wang Y, Yao H, Kim SB, Geng CZ, Rodriguez Pantigoso W, Ramirez Godinez FJ, Song C, Ching Chang Y, Antoniazzi A, Chen SC, Li Z, Nowecki Z, Lim J, Mathias E, Sato Y, Lu W, Abdel-Monem H, Untch M, Geyer CE Jr; DESTINY-Breast05 Trial Investigators. Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer. N Engl J Med. 2026 Feb 26;394(9):845-857. doi: 10.1056/NEJMoa2514661. Epub 2025 Dec 10.
- Boman C, Tranchell C, Liu X, Eriksson Bergman L, Toli MA, Bergh J, Foukakis T, Matikas A. Prognosis After Pathologic Complete Response to Neoadjuvant Therapy in Early-Stage Breast Cancer: A Population-Based Study. J Natl Compr Canc Netw. 2025 Mar 12;23(4):e247093. doi: 10.6004/jnccn.2024.7093.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Trastuzumab deruxtecan | Monoclonal antibody | 5.4 mg/kg | Intravenous |
| Comparator | Trastuzumab emtansine | Other / unclassified | 3.6 mg/kg | Intravenous |