Positive topline results from a planned interim analysis of the DESTINY-Breast05 phase 3 trial showed ENHERTU^® (trastuzumab deruxtecan) demonstrated a highly statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS) versus trastuzumab emtansine (T-DM1) in patients with HER2 positive early breast cancer with residual invasive disease in the breast or axillary lymph nodes after neoadjuvant treatment and high risk of disease recurrence. This is the second positive phase 3 trial of ENHERTU in the HER2 positive early breast cancer setting following positive results from the DESTINY-Breast11 phase 3 neoadjuvant trial earlier this year.

Overall survival (OS) was not mature at the time of this planned interim analysis and will be assessed at a subsequent analysis.

ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Currently, approximately half of patients with HER2 positive early breast cancer have residual disease following neoadjuvant treatment, putting them at an increased risk of disease recurrence.^1-7 Despite receiving additional treatment in the post-neoadjuvant setting, some patients still ultimately experience tumor progression to metastatic disease. ^8,9 New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression and improve long-term outcomes for more patients.^10,11

“In patients with early breast cancer with residual disease following neoadjuvant treatment, it is critical to optimize treatment as this represents the last opportunity to prevent progression to metastatic disease,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “The results of DESTINY-Breast05 demonstrate that treatment with ENHERTU following surgery increases the length of time patients are able to live free of invasive disease compared to the existing standard of care, potentially offering patients with HER2 positive early breast cancer a new treatment approach in this curative-intent setting.”

“This landmark trial is the first to directly compare ENHERTU and T-DM1 in early breast cancer and the results clearly show that ENHERTU delivers superior outcomes, indicating that it may be a better option for patients with high risk HER2 positive early breast cancer in the post-neoadjuvant setting,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “These results from DESTINY-Breast05, coupled with DESTINY-Breast11, underscore our commitment to moving ENHERTU into early-stage HER2 positive breast cancer where patients can achieve sustained long-term outcomes, increasing the opportunity for cure.”

The safety profile of ENHERTU observed in DESTINY-Breast05 was consistent with its known profile with no new safety concerns identified.

Data from DESTINY-Breast05 (Abstract #LBA1) and DESTINY-Breast11 (Abstract #291O) will be presented during Presidential Symposium I on Saturday, October 18 at the upcoming 2025 European Society for Medical Oncology (#ESMO25) Congress. The DESTINY-Breast05 data also will be shared with global regulatory authorities.

DESTINY-Breast05 was conducted in collaboration with the National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP), the German Breast Group (GBG), Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-B) and SOLTI Breast Cancer Research Group.