The EU approves Enhertu for HER2-positive early breast cancer with residual disease after neoadjuvant therapy, based on DESTINY-Breast05 results.
Written By: Umesh Hanumante, M. Pharm (RA)
Reviewed By: Pharmacally Editorial Team
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has received European Commission approval as an adjuvant monotherapy for adults with resected HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane-based chemotherapy and HER2-targeted treatment. The decision, based on Phase III DESTINY-Breast05 results, introduces a new treatment option for patients at high risk of recurrence after pre-surgical therapy.
Approval Targets Patients at High Risk of Recurrence
Neoadjuvant treatment aims to eliminate invasive cancer before surgery, but some patients retain disease in the breast or axillary lymph nodes. This residual disease signals a higher risk of recurrence and creates a need for effective post-surgical treatment.
The European Commission’s decision follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP). It marks the first EU approval of Enhertu in the curative-intent early breast cancer setting.
DESTINY-Breast05 Demonstrated Improved Disease Control
The global, randomised, open-label Phase III DESTINY-Breast05 trial (NCT04622319) enrolled 1,635 patients with HER2-positive early breast cancer and residual invasive disease following neoadjuvant therapy. Participants had a high risk of recurrence, defined as initially inoperable disease before neoadjuvant treatment or pathologically positive axillary lymph nodes after treatment.
Patients received Enhertu at 5.4 mg/kg or trastuzumab emtansine (T-DM1). The primary endpoint was investigator-assessed invasive disease-free survival (IDFS), measuring the time from randomisation to the first invasive local, axillary or distant recurrence, or death from any cause.
Enhertu reduced the hazard of invasive disease recurrence or death by 53% compared with T-DM1 (hazard ratio, 0.47; 95% confidence interval [CI], 0.34–0.66; p<0.0001).
At three years, the estimated IDFS rate was 92.4% with Enhertu (95% CI, 89.7–94.4), compared with 83.7% with T-DM1 (95% CI, 80.2–86.7). The 8.7-percentage-point difference indicates a clinically meaningful improvement in invasive disease control against an active comparator.
Investigator Highlights the Importance of Recurrence Prevention
Sibylle Loibl, lead investigator of DESTINY-Breast05, emphasised the importance of reducing recurrence risk for patients with residual invasive disease after neoadjuvant treatment. She said the more than 50% reduction in risk observed with Enhertu has the potential to change treatment for eligible patients.
The findings support Enhertu’s role in this specific high-risk population. However, IDFS is distinct from overall survival, and the reported results do not independently establish an overall-survival benefit. Longer follow-up will be important to clarify the durability of the treatment effect.
Safety and Commercial Implications
The companies reported that Enhertu’s safety profile in DESTINY-Breast05 was consistent with its established profile, with no new safety concerns identified. This does not mean treatment is risk-free; clinicians must consider the product information and monitor patients for recognised adverse reactions, including interstitial lung disease and pneumonitis.
The approval also triggers a US$75 million milestone payment from AstraZeneca to Daiichi Sankyo under their collaboration agreement. Daiichi Sankyo recognises Enhertu sales in most EU territories.
Clinical Interpretation
The EU approval extends Enhertu into an earlier treatment setting for eligible patients whose HER2-positive breast cancer remains invasive after neoadjuvant therapy and surgery. DESTINY-Breast05 demonstrated improved three-year IDFS over T-DM1, supporting the treatment’s potential to reduce recurrence risk in this defined population. Whether this improvement translates into longer overall survival remains an important question for continued follow-up.
References
Enhertu approved in the EU as adjuvant treatment for patients with residual disease after neoadjuvant treatment for HER2-positive early breast cancer, Astra Zeneca, 27 October 2026
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), ClinicalTrials.gov ID NCT04622319
About the Writer
Umesh Hanumante (M.Pharm) (LinkedIn) is a pharmacy professional and healthcare writer with a background in Regulatory Affairs, pharmaceutical innovation, and clinical research. He has around two years of industry experience as an Executive PMT at Troikaa Pharmaceuticals Ltd and qualified GPAT 2024. His areas of interest include regulatory compliance, dossier preparation, clinical trials, emerging therapies, and advancements in the global pharmaceutical and healthcare sector.