At a Glance
- EMA validated ENHERTU® Type II Variation MAA on Feb 19, 2026, as monotherapy for post-neoadjuvant HER2+ (IHC 3+/ISH+) early breast cancer with residual disease.
- DESTINY-Breast05 phase 3 trial showed ENHERTU (5.4 mg/kg) beat T-DM1 on IDFS (n=1,635; data in NEJM/ESMO 2025).
- High-risk patients have residual invasive disease post-neoadjuvant, and CHMP scientific review is now underway.
- Additional EU filings include ENHERTU + pertuzumab (DESTINY-Breast09) and HER2+ solid tumors (DESTINY-PanTumor02, etc.).
Written By: Sana Khan BPharm
Reviewed By: Pharmacally Editorial Team
The European Medicines Agency (EMA) advanced ENHERTU® (trastuzumab deruxtecan), a HER2-directed antibody-drug conjugate (ADC) from Daiichi Sankyo and AstraZeneca.
On February 19, 2026, EMA validated a Type II Variation application. It seeks approval for ENHERTU as monotherapy in adults with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease after neoadjuvant HER2-targeted treatment.
This starts CHMP scientific review, based on phase 3 DESTINY-Breast 05 data (NCT04622319).
Breakthrough from DESTINY-Breast05 Trial
Results were shared at the 2025 ESMO Congress and in The New England Journal of Medicine.
This global trial randomized 1,635 patients across Asia, Europe, North America, Oceania, and South America.
Patients had HER2-positive early breast cancer with residual disease in breast or axillary nodes after neoadjuvant therapy signaling high recurrence risk (e.g., inoperable pre-neoadjuvant or positive nodes post).
ENHERTU (5.4 mg/kg) beat T-DM1 on primary endpoint: invasive disease-free survival (IDFS), time to invasive recurrence or death. The win was statistically significant and clinically meaningful.
Key secondary endpoints: disease-free survival, overall survival, distant recurrence-free interval, brain metastases-free interval, safety.
“Patients with residual disease need better options post-neoadjuvant,” said Ken Takeshita, MD, Global Head of R&D, Daiichi Sankyo. He called this a step to bring ENHERTU earlier and cut metastatic risk.
ENHERTU’s Expanding Global Approvals and Pipeline
ENHERTU holds approvals in over 90 countries for metastatic HER2-positive breast cancer (post-prior anti-HER2), HER2-low breast cancer (DESTINY-Breast03/04), and HR-positive/HER2-low/ultralow (DESTINY-Breast06). It’s also approved for HER2-mutant NSCLC, HER2-positive gastric/GEJ cancer, and select HER2-positive solid tumors.
In the EU, additional submissions are pending:
With pertuzumab for first-line unresectable/metastatic HER2-positive breast cancer (DESTINY-Breast09).
For previously treated HER2-positive unresectable/metastatic solid tumors (DESTINY-PanTumor02, DESTINY-CRC02, DESTINY-Lung01).
Why This Matters for HER2-Positive Early Breast Cancer
Breast cancer ranks as the second most common cancer worldwide, with over 2 million cases and 665,000 deaths in 2022; Europe sees 557,000 cases and 144,000 deaths yearly.
About 20% are HER2-positive, driven by HER2 gene amplification, leading to aggressive disease. Neoadjuvant therapy aims for pathologic complete response (pCR), a strong survival predictor, but 50% of patients have residual disease, elevating recurrence odds.
Post-neoadjuvant treatment like T-DM1 offers limited CNS protection, and metastatic progression drops 5-year survival from 90% to 30%.
ENHERTU targets this gap, using Daiichi Sankyo’s DXd ADC technology: a HER2 antibody linked to topoisomerase I inhibitor payloads (DXd) via cleavable tetrapeptide linkers for precise tumor delivery.
Daiichi Sankyo and AstraZeneca’s program tests ENHERTU across HER2 cancers, alone or combined.
Reference
ENHERTU® Type II Variation Application Validated in the EU as Post-Neoadjuvant Treatment for Patients with HER2 Positive Early Breast Cancer, 19 February 2026, 20260219_E.pdf
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, https://clinicaltrials.gov/study/NCT04622319
Loibl S et al, DESTINY-Breast05 Trial Investigators. Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer. N Engl J Med. 2025 Dec 10. Epub ahead of print. PMID: 41370739. https://doi.org/10.1056/nejmoa2514661