MEDISEARCHER NEWS
European Union · Breast cancer · 28 October 2026
The European Commission has approved Enhertu (trastuzumab deruxtecan) for certain adults with HER2-positive early breast cancer, moving the medicine into a curative-intent setting where treatment is designed to prevent the cancer from returning after surgery.
The new indication applies to adults with resected HER2-positive breast cancer who still have residual invasive disease after receiving taxane-based chemotherapy and HER2-targeted treatment before surgery.
In the Phase III DESTINY-Breast05 trial, Enhertu reduced the relative risk of invasive disease recurrence or death by 53% compared with trastuzumab emtansine (T-DM1), the established post-surgery treatment for this high-risk group.
In brief
- The European Commission has approved Enhertu for adults with resected HER2-positive early breast cancer who have residual invasive disease after pre-surgery taxane-based and HER2-targeted treatment.
- This is Enhertu’s first EU approval in the curative-intent early breast cancer setting.
- In the 1,635-patient Phase III DESTINY-Breast05 trial, Enhertu reduced the relative risk of invasive disease recurrence or death by 53% compared with T-DM1.
- At three years, 92.4% of patients receiving Enhertu were alive without invasive disease compared with 83.7% receiving T-DM1.
- Enhertu also carries an important risk of interstitial lung disease. Drug-related ILD occurred in 9.6% of Enhertu patients versus 1.6% receiving T-DM1, and two patients in the Enhertu group died from ILD.
- EU marketing authorisation does not mean access will be identical across member states. Pricing and reimbursement decisions still take place through national health systems.
What has the EU approved?
Enhertu can now be used as a single-agent adjuvant treatment for adults with surgically removed HER2-positive breast cancer who have residual invasive disease after receiving taxane-based chemotherapy and HER2-targeted therapy before surgery.
The European Commission decision follows a positive opinion adopted by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) on 17 September 2026.
Enhertu, also known as trastuzumab deruxtecan or T-DXd, is a HER2-directed antibody-drug conjugate. It combines an antibody designed to recognise HER2 with a chemotherapy payload that is delivered to cancer cells.
The medicine is already established in several forms of advanced or metastatic HER2-related breast cancer. The significance of the new approval is that Enhertu is now moving much earlier in treatment, when the objective is to prevent recurrence and maximise the possibility of long-term cure.
Who does the new Enhertu approval apply to?
The new indication concerns a specific group of patients with HER2-positive early breast cancer.
These patients have received treatment before surgery — known as neoadjuvant therapy — using a taxane and HER2-targeted medicine. Their cancer is then surgically removed.
Some patients have no invasive cancer remaining in the breast or lymph nodes when the removed tissue is examined. This is known as a pathological complete response.
Others still have invasive cancer cells remaining despite the pre-surgery treatment. This is called residual invasive disease.
Residual disease matters because these patients face a higher risk of the breast cancer returning and therefore receive additional treatment after surgery.
Until now, T-DM1 has been an important standard post-neoadjuvant treatment for this group in Europe. DESTINY-Breast05 directly compared Enhertu with T-DM1 rather than with placebo.
What did DESTINY-Breast05 find?
DESTINY-Breast05 was a global, randomized, open-label Phase III trial involving 1,635 patients with HER2-positive early breast cancer who had residual invasive disease after neoadjuvant therapy and were considered at high risk of recurrence.
Patients received either Enhertu at 5.4 mg/kg or T-DM1.
The primary outcome was invasive disease-free survival, which measures the time before an invasive local, regional or distant recurrence of cancer, or death.
Enhertu reduced the relative risk of invasive disease recurrence or death by 53% compared with T-DM1.
The hazard ratio was 0.47, with a 95% confidence interval of 0.34 to 0.66.
How many patients remained free of invasive disease?
At three years, estimated invasive disease-free survival was:
- 92.4% among patients receiving Enhertu; and
- 83.7% among patients receiving T-DM1.
That difference helps put the headline 53% relative risk reduction into context.
A 53% relative reduction does not mean that 53% more patients were cured or that cancer recurrence was eliminated in half of all patients.
Instead, it describes the relative difference in the rate of invasive disease recurrence or death between the two treatment groups during the trial period.
The trial also found a significant improvement in disease-free survival, while distant recurrence was reduced compared with T-DM1.
Why is treating residual disease so important?
HER2-positive breast cancer is driven by overexpression or amplification of the HER2 protein, which promotes cancer-cell growth.
Modern HER2-targeted therapies have dramatically improved outcomes, particularly when treatment successfully eliminates invasive disease before surgery.
But patients whose surgical specimens still contain invasive cancer after neoadjuvant treatment remain at greater risk of recurrence.
Post-surgery treatment therefore provides another opportunity to eliminate microscopic cancer cells that may remain elsewhere in the body before they can develop into recurrent or metastatic disease.
This is why moving an effective medicine such as Enhertu from advanced cancer into the early-disease setting is potentially important: the treatment is being used when preventing recurrence may still contribute to cure.
Does Enhertu improve overall survival?
The strongest current evidence from DESTINY-Breast05 concerns invasive disease-free survival rather than mature overall survival.
The trial has demonstrated a substantial reduction in invasive recurrence or death compared with T-DM1, but longer follow-up remains important for determining the eventual effect on overall survival.
This distinction matters because preventing recurrence is a clinically important outcome in early breast cancer, but it should not automatically be interpreted as proof of an equivalent reduction in the risk of dying from breast cancer.
What are the main side effects of Enhertu?
Enhertu has an established safety profile from its use across several cancer settings, but the DESTINY-Breast05 results also highlight important risks.
Common adverse events reported with Enhertu included:
- nausea;
- constipation;
- decreased neutrophil counts; and
- vomiting.
The particularly important safety issue is interstitial lung disease (ILD), a group of inflammatory and fibrotic conditions affecting lung tissue that is a known risk associated with Enhertu.
In DESTINY-Breast05, adjudicated drug-related ILD occurred in 9.6% of patients receiving Enhertu compared with 1.6% receiving T-DM1.
Two patients in the Enhertu group died from interstitial lung disease.
Patients receiving Enhertu therefore require monitoring for respiratory symptoms such as new or worsening cough, shortness of breath or fever. Suspected ILD requires prompt medical assessment and may require interruption or permanent discontinuation of treatment depending on severity.
How does Enhertu compare with T-DM1?
Both Enhertu and T-DM1 are HER2-directed antibody-drug conjugates, but they use different antibodies, linkers and chemotherapy payloads.
T-DM1 became an important standard treatment for patients with residual HER2-positive disease after neoadjuvant therapy because it substantially reduced recurrence compared with trastuzumab alone.
DESTINY-Breast05 therefore tested Enhertu against an effective active treatment rather than an untreated control group.
The 53% relative reduction in invasive recurrence or death versus T-DM1 is consequently particularly noteworthy, although the different toxicity profiles of the two medicines also need to be considered when treatment decisions are made.
Is Enhertu now available everywhere in the EU?
The European Commission approval creates a centrally authorised indication across the European Union, but that does not mean patients in every member state will obtain Enhertu for this use immediately.
National health systems still make decisions about pricing, reimbursement, health-technology assessment and how a medicine is incorporated into clinical practice.
The timing of practical access can therefore differ between countries such as Germany, France, Italy, Spain, the Netherlands, Ireland, Sweden, Poland and other EU member states.
The European approval is consequently the beginning of the next stage of the access process rather than the end of it.
MediSearcher will monitor national reimbursement and patient-access decisions as they emerge.
Why the EU approval matters
Enhertu has become an important treatment across several forms of advanced HER2-positive and HER2-expressing breast cancer.
The new approval represents a different stage in that development.
Instead of treating cancer after it has become advanced or metastatic, Enhertu can now be used in eligible patients with early-stage disease after surgery, when treatment is intended to stop residual cancer from returning.
DESTINY-Breast05 also compared the medicine against T-DM1, an established effective treatment, and still demonstrated a substantial improvement in invasive disease-free survival.
For patients with residual HER2-positive disease after pre-surgery treatment, the results could therefore change the post-surgery treatment pathway across Europe.
The remaining questions will include longer-term survival outcomes, continued monitoring of interstitial lung disease and, importantly for European patients, how quickly individual countries fund and implement the newly approved indication.
Reviewed by: Dr Mattias Hagman, PhD
Editorial review: This article was reviewed for regulatory accuracy, interpretation of the DESTINY-Breast05 Phase III results, relative versus absolute treatment effects, safety findings and the distinction between EU marketing authorisation and national patient access.
Last reviewed: 28 October 2026
Sources and verification
MediSearcher reviewed the following primary and authoritative sources when preparing this article:
- European Commission — Union Register of medicinal products and Commission decisions
- European Medicines Agency — Enhertu variation to marketing authorisation for early HER2-positive breast cancer
- New England Journal of Medicine / PubMed — Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer
- ClinicalTrials.gov — DESTINY-Breast05 Phase III trial (NCT04622319)
This article is for general informational purposes only and is not medical advice. Breast cancer treatment depends on tumor characteristics, previous treatment, response to therapy, other medical conditions and individual circumstances. Patients should discuss treatment options and potential risks with their oncology team.