drugset / Trial / NCT03734029
Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]
RandomizedParallel-groupOpen-labelTreatment
Summary
This study will compare DS-8201a to physician choice standard treatment. Participants must have HER2-low breast cancer that has been treated before. Participants' cancer: * Cannot be removed by an operation * Has spread to other parts of the body
Timeline
- Start
- 2018-12-27
- Primary completion
- 2022-01-11
- Completion
- 2026-05-19
Outcome
Met primary endpoint
paper The study met its primary efficacy end point of progression-free survival (PFS) PMID 36780610 ↗
registry Trastuzumab Deruxtecan (T-DXd) vs Physician's Choice; p <0.0001 NCT03734029 ↗
release “In the primary endpoint analysis for DESTINY-Breast04, Enhertu demonstrated a 49% reduction in the risk of disease progression or death” astrazeneca.com ↗
release “Based on DESTINY-Breast04 results which showed AstraZeneca and Daiichi Sankyo’s Enhertu reduced risk of disease progression or death by 50%” astrazeneca.com ↗
release “In DESTINY-Breast04, Enhertu reduced the risk of disease progression or death by 50% versus physician’s choice of chemotherapy” astrazeneca.com ↗
Publications
- Results Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. doi: 10.1056/NEJMoa2203690. Epub 2022 Jun 5.
- Iyengar AR, Downs EP, Mehta S, Rangarajan N, Woo MS, Sredni ST, Donato RD, Simsek S, Wilson DM, Krieser K, Patzke EB, Kyek N, Anderson C, Wagner T, Hipp J, Nassar A, Barman H. HER2-Ultralow: Prevalence, Characteristics, and Treatment Choices Among Advanced Breast Cancer Patients With Tumors Initially Scored as IHC 0. Breast J. 2026;2026(1):e7212120. doi: 10.1155/tbj/7212120.
- Modi S, Jacot W, Iwata H, Park YH, Vidal Losada M, Li W, Tsurutani J, Ueno NT, Zaman K, Prat A, Papazisis K, Rugo HS, Yamashita T, Harbeck N, Im SA, De Laurentiis M, Pierga JY, Wang X, Gombos A, Tokunaga E, Orbegoso Aguilar C, Yung L, Xiao F, Cheng Y, Cameron D. Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial. Nat Med. 2025 Dec;31(12):4205-4213. doi: 10.1038/s41591-025-03981-4. Epub 2025 Oct 8.
- Ueno NT, Cottone F, Dunton K, Jacot W, Yamashita T, Sohn J, Tokunaga E, Prat A, Tsurutani J, Park YH, Rugo HS, Xu B, Cardoso F, Mitri Z, Mahtani R, Aguilar CO, Xiao F, Harbeck N, Cameron DA, Modi S. Patient-reported outcomes from DESTINY-Breast04: trastuzumab deruxtecan versus physician's choice of chemotherapy in patients with HER2-low mBC. Oncologist. 2025 May 8;30(5):oyaf048. doi: 10.1093/oncolo/oyaf048.
- Yamashita T, Sohn JH, Tokunaga E, Niikura N, Park YH, Lee KS, Chae YS, Xu B, Wang X, Im SA, Li W, Lu YS, Aguilar CO, Nishijima S, Nishiyama Y, Sugihara M, Modi S, Tsurutani J. Trastuzumab deruxtecan versus treatment of physician's choice in previously treated Asian patients with HER2-low unresectable/metastatic breast cancer: subgroup analysis of the DESTINY-Breast04 study. Breast Cancer. 2024 Sep;31(5):858-868. doi: 10.1007/s12282-024-01600-7. Epub 2024 Jun 17.
- Ma R, Shi Y, Yan R, Yin S, Bu H, Huang J. Efficacy and safety of trastuzumab deruxtecan in treating human epidermal growth factor receptor 2-low/positive advanced breast cancer:A meta-analysis of randomized controlled trials. Crit Rev Oncol Hematol. 2024 Apr;196:104305. doi: 10.1016/j.critrevonc.2024.104305. Epub 2024 Mar 3.
- Jhaveri K, Eli LD, Wildiers H, Hurvitz SA, Guerrero-Zotano A, Unni N, Brufsky A, Park H, Waisman J, Yang ES, Spanggaard I, Reid S, Burkard ME, Vinayak S, Prat A, Arnedos M, Bidard FC, Loi S, Crown J, Bhave M, Piha-Paul SA, Suga JM, Chia S, Saura C, Garcia-Saenz JA, Gambardella V, de Miguel MJ, Gal-Yam EN, Rapael A, Stemmer SM, Ma C, Hanker AB, Ye D, Goldman JW, Bose R, Peterson L, Bell JSK, Frazier A, DiPrimeo D, Wong A, Arteaga CL, Solit DB. Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial. Ann Oncol. 2023 Oct;34(10):885-898. doi: 10.1016/j.annonc.2023.08.003. Epub 2023 Aug 18.
- Rugo HS, Crossno CL, Gesthalter YB, Kelley K, Moore HB, Rimawi MF, Westbrook KE, Buys SS. Real-World Perspectives and Practices for Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use in Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer. JCO Oncol Pract. 2023 Aug;19(8):539-546. doi: 10.1200/OP.22.00480. Epub 2023 May 19.
- Narayan P, Dilawari A, Osgood C, Feng Z, Bloomquist E, Pierce WF, Jafri S, Kalavar S, Kondratovich M, Jha P, Ghosh S, Tang S, Pazdur R, Beaver JA, Amiri-Kordestani L. US Food and Drug Administration Approval Summary: Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer. J Clin Oncol. 2023 Apr 10;41(11):2108-2116. doi: 10.1200/JCO.22.02447. Epub 2023 Feb 13.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Capecitabine | Small molecule | — | — |
| Comparator | Eribulin | Small molecule | — | — |
| Comparator | Gemcitabine | Small molecule | — | — |
| Comparator | Nab-paclitaxel | Small molecule | — | — |
| Comparator | Paclitaxel | Small molecule | — | — |
| Subject | Trastuzumab deruxtecan | Monoclonal antibody | 5.4 mg/kg | Intravenous |