Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial
In DESTINY-Breast04 ( NCT03734029 ), trastuzumab deruxtecan (T-DXd) significantly improved overall survival (OS) and progression-free survival compared with treatment of physician's choice of chemotherapy (TPC) for patients with human epidermal growth factor receptor 2-low (HER2-low) (immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization-negative) metastatic breast cancer. After an extended median follow-up of 32.0 months, median OS in the overall cohort was 22.9 months for T-DXd and 16.8 months for TPC (hazard ratio 0.69; 95% confidence interval 0.55-0.86). For the hormone receptor-positive cohort, median OS was 23.9 and 17.6 months for T-DXd and TPC, respectively (hazard ratio 0.69; 95% confidence interval 0.55-0.87). Median OS also favored T-DXd in exploratory analyses of hormone receptor-negative, estrogen receptor IHC 1%-10% and estrogen receptor IHC >10% cohorts. The overall safety profile of T-DXd was acceptable and generally manageable. Results confirm T-DXd as standard of care after prior chemotherapy in patients with HER2-low metastatic breast cancer. ClinicalTrials.gov identifier: NCT03734029 .
Authors
- María Vidal (ORCID: https://orcid.org/0000-0003-1992-5727)
- Winnie Yeo (ORCID: https://orcid.org/0000-0002-0863-8469)
- David Cameron (ORCID: https://orcid.org/0000-0002-2717-7979)
- Eriko Tokunaga (ORCID: https://orcid.org/0000-0002-1640-5315)
- Lotus Yung
- Junji Tsurutani (ORCID: https://orcid.org/0000-0002-6260-6943)
- Jean‐Yves Pierga (ORCID: https://orcid.org/0000-0002-2863-9995)
- Michelino De Laurentiis (ORCID: https://orcid.org/0000-0001-9009-1572)
- Nadia Harbeck (ORCID: https://orcid.org/0000-0002-9744-7372)
- Shanu Modi (ORCID: https://orcid.org/0000-0001-6427-7373)
- Khalil Zaman (ORCID: https://orcid.org/0000-0002-2997-527X)
- William Jacot (ORCID: https://orcid.org/0000-0001-7834-061X)
- Hiroji Iwata
- Konstantinos Papazisis (ORCID: https://orcid.org/0000-0002-1048-2715)
- Seock‐Ah Im (ORCID: https://orcid.org/0000-0002-5396-6533)
- Wei Li (ORCID: https://orcid.org/0000-0002-7267-6494)
- Naoto Tada Ueno (ORCID: https://orcid.org/0000-0002-0166-7275)
- Aleix Prat (ORCID: https://orcid.org/0000-0003-2377-540X)
- Hope S. Rugo (ORCID: https://orcid.org/0000-0001-6710-4814)
- Feng Xiao (ORCID: https://orcid.org/0000-0002-9774-8300)
- Xiaojia Wang (ORCID: https://orcid.org/0000-0002-7005-0842)
- Andrea Gombos
- Yingkai Cheng
- Cecilia Orbegoso Aguilar
- Toshinari Yamashita
Institutions
- SHOWA Medical University (JP)
- Memorial Sloan Kettering Cancer Center (US)
- Inserm (FR)
- Jilin University (CN)
- Breast Cancer Research Foundation (US)
- Université Paris Cité (FR)
- Institut Jules Bordet (BE)
- Samsung Medical Center (KR)
- Edinburgh Cancer Research (GB)
- Seoul National University Hospital (KR)
- Kanagawa Prefectural Hospital Organization (JP)
- Nagoya City University (JP)
- Cancer Center of Hawaii (US)
- National Hospital Organization Kyushu Cancer Center (JP)
- Zhejiang Cancer Hospital (CN)
- Euromedica (GR)
- First Hospital of Jilin University (CN)
- Institut de Recherche en Cancérologie de Montpellier (FR)
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Daiichi Sankyo (United States) (US)
- UCSF Helen Diller Family Comprehensive Cancer Center (US)
- Kanagawa Cancer Center
- Institut Curie (FR)
- Ludwig-Maximilians-Universität München (DE)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Nature Medicine
- Published
- 2025-10-08
- DOI
- https://doi.org/10.1038/s41591-025-03981-4
- Citations
- 13
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 13.59
Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Bayer
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- F. Hoffmann-La Roche
- Genomic Health
- Les Laboratories Pierre Fabre
- Mylan
- BeiGene
- Sysmex Corporation
- Puma Biotechnology
- Seagen
- Eisai
- Papua New Guinea University of Technology
- Daewoong Pharmaceutical Company
- European Society for Medical Oncology
- Ipsen
- Genentech
- Novartis Pharma
- Chugai Pharmaceutical
- Daiichi Sankyo Europe