EMA Validation of ENHERTU Breast Cancer Treatment for Post-Neoadjuvant Therapy
EMA Validates ENHERTU Breast Cancer Treatment Variation
The European Medicines Agency (EMA) has validated a Type II Variation marketing authorization application for ENHERTU breast cancer treatment, specifically ENHERTU (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate (ADC), as monotherapy for adults with HER2-positive (immunohistochemistry [IHC] 3+ or in-situ hybridization [ISH]+) breast cancer exhibiting residual invasive disease after neoadjuvant HER2-targeted treatment. This application draws from the DESTINY-Breast05 phase 3 trial, where ENHERTU reduced the risk of invasive disease-free survival (IDFS) events—defined as invasive local, axillary, or distant recurrence or death—by 53% compared to trastuzumab emtansine (T-DM1). ENHERTU breast cancer treatment could establish itself as a new standard of care in this high-risk early breast cancer setting, addressing unmet needs for patients with residual disease post-neoadjuvant therapy. Details from Daiichi Sankyo’s press release highlight the trial’s impact.
DESTINY-Breast05 Delivers 53% IDFS Risk Cut
The DESTINY-Breast05 trial provides compelling evidence of ENHERTU breast cancer treatment efficacy, demonstrating a statistically significant and clinically meaningful improvement in investigator-assessed IDFS over T-DM1 in patients with HER2-positive early breast cancer and residual invasive disease following neoadjuvant therapy. Enrolling 1,635 patients across Asia, Europe, North America, Oceania, and South America, the randomized, open-label phase 3 study evaluated ENHERTU at 5.4 mg/kg against T-DM1 in those at high recurrence risk, defined by inoperable cancer pre-neoadjuvant therapy or pathologically positive axillary nodes post-therapy.
Key secondary endpoints, including disease-free survival, overall survival, distant recurrence-free interval, and brain metastases-free interval, alongside safety profiles, further underscore the trial’s robust findings, which were presented at the 2025 European Society for Medical Oncology Congress and published in The New England Journal of Medicine. This positions ENHERTU as a potential advancement in reducing recurrence risks, particularly given that approximately half of neoadjuvant-treated patients fail to achieve pathologic complete response (pCR), heightening their vulnerability to invasive disease or death.
High-Risk Patient Selection in Global Trial
DESTINY-Breast05 employed a global, multicenter, randomized, open-label design to rigorously assess ENHERTU’s role in a post-neoadjuvant context, with IDFS as the primary endpoint measured from randomization to the first IDFS event. Patients were selected based on high recurrence risk after neoadjuvant HER2-targeted therapy and surgery, reflecting a critical population where current options like T-DM1 show limited impact on central nervous system recurrence. This builds on the epidemiology of HER2-positive breast cancer, which affects about one in five cases and is linked to aggressive disease due to HER2 gene amplification; globally, breast cancer caused over 665,000 deaths in 2022, with Europe seeing 557,000 annual diagnoses and 144,000 fatalities. Post-neoadjuvant therapy emerges as a pivotal intervention point to avert progression to metastatic disease, where five-year survival plummets from nearly 90% to around 30%, justifying the need for innovative ADCs like ENHERTU.
Reshaping HEOR and Payer Strategies
Approval of ENHERTU breast cancer treatment in this post-neoadjuvant indication could introduce a therapy with superior IDFS benefits, potentially lowering long-term costs associated with metastatic recurrence and its intensive resource demands. This 53% risk reduction versus T-DM1 may support value-based pricing strategies, emphasizing IDFS gains in health technology assessments, particularly as ENHERTU expands across HER2-expressing cancers via ongoing trials like DESTINY-Breast09 and DESTINY-PanTumor02.
For European payers, integration into early breast cancer pathways could enhance cost-effectiveness analyses by delaying progression, aligning with trends toward ADCs as standards in oncology where unmet needs persist despite neoadjuvant advances. This announcement not only signals regulatory momentum—amid ENHERTU’s approvals in over 90 countries for metastatic settings, ultimately aiming to optimize patient outcomes while balancing reimbursement pressures in resource-constrained systems.
