Enhertu^® (trastuzumab deruxtecan) has been approved in the European Union (EU) as a monotherapy for the adjuvant treatment of adult patients with resected HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization [ISH]+) breast cancer who have residual invasive disease after neoadjuvant taxane-based and HER2 targeted treatment.

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/NYSE: AZN).

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use of the European Medicines Agency and is based on results from the DESTINY-Breast05 phase 3 trial presented at the 2025 European Society for Medical Oncology (#ESMO25) Congress and subsequently published in The New England Journal of Medicine.

In DESTINY-Breast05, Enhertu significantly reduced the risk of invasive disease recurrence or death (invasive disease-free survival [IDFS]) by 53% (hazard ratio [HR]=0.47; 95% confidence interval [CI]: 0.34-0.66; p<0.0001) compared to trastuzumab emtansine (T-DM1) in patients with HER2 positive breast cancer with residual invasive disease following neoadjuvant therapy. Enhertu demonstrated a three-year IDFS rate of 92.4% (95% CI: 89.7-94.4) and 83.7% with T-DM1 (95% CI: 80.2-86.7). Data also showed that Enhertu significantly reduced the risk of disease recurrence or death (disease-free survival [DFS]) by 53% (HR=0.47; 95% CI: 0.34-0.66; p<0.0001) compared to T-DM1. Results showed a three-year DFS rate of 92.3% (95% CI: 89.5-94.3) in the Enhertu arm and 83.5% with T-DM1 (95% CI: 79.9-86.4).

“For patients with HER2 positive early breast cancer and residual invasive disease after neoadjuvant therapy, reducing the risk of disease recurrence is critical for sustained long-term outcomes,” said Sibylle Loibl, MD, PhD, GBG (German Breast Group) and Goethe University Medicine Frankfurt, Frankfurt am Main and lead investigator of the DESTINY-Breast05 trial. “The EU approval of trastuzumab deruxtecan, which demonstrated a more than 50% reduction in risk of recurrence compared to standard of care in DESTINY-Breast05, has the potential to change how we treat eligible patients in this setting.”

In DESTINY-Breast05, the safety profile of Enhertu was consistent with the known profile with no new safety concerns identified. Grade 3 or grade 4 adverse reactions from a pooled safety analysis of 4,146 patients who received at least one dose of Enhertu (5.4 mg/kg) in clinical studies across multiple tumor types included neutropenia (18.7%), anemia (8.2%), fatigue (7.4%), leukopenia (6.6%), thrombocytopenia (5.4%), lymphopenia (5.0%), nausea (4.5%), increased transaminases (3.3%), hypokalemia (3.1%), pancytopenia (2.8%), diarrhea (2.1%), vomiting (2.0%), decreased appetite (1.4%) and pneumonia (1.2%). Grade 5 adverse reactions occurred in 0.9% of patients, including interstitial lung disease (ILD)/pneumonitis (0.8%).

“By bringing Enhertu into the adjuvant setting, we are advancing this treatment option earlier in the course of disease for patients with HER2 positive early breast cancer,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “This first approval of Enhertu in early breast cancer in the EU reflects our continued commitment to bringing innovative medicines into earlier treatment settings, where there is significant potential to improve long-term outcomes for patients.”

“The goal of treatment in early breast cancer is to help as many patients as possible achieve cure. Unfortunately, despite treatment advances, some patients still face recurrence in the long-term,” said Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca. “The approval of Enhertu in the adjuvant setting for patients with residual disease after neoadjuvant treatment has the potential to establish a new benchmark in this curative-intent setting, with more than 92% of patients alive and free of invasive disease at three years.”

Enhertu (5.4 mg/kg) is now approved in more than 35 countries/regions worldwide for the adjuvant treatment of adult patients with HER2 positive breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment based on the DESTINY-Breast05 trial.

Financial Considerations
Following this approval in the EU, an amount of $75 million is due from AstraZeneca to Daiichi Sankyo as a milestone payment for the adjuvant HER2 positive early breast cancer indication. Sales of Enhertu in most EU territories are recognized by Daiichi Sankyo. For further details on the financial arrangements, please consult the collaboration agreement from March 2019.