For patients with HER2-positive early breast cancer, completing chemotherapy and undergoing surgery does not always mean the end of treatment. When cancer cells remain in the breast or lymph nodes after preoperative therapy, the risk of recurrence becomes a major concern, even when the visible tumor has been removed.
Now, a new European approval could change how oncologists approach this critical stage of treatment.
On October 27, 2026, the European Commission approved trastuzumab deruxtecan, developed by Daiichi Sankyo and AstraZeneca, as adjuvant monotherapy for adults with resected HER2-positive early breast cancer who have residual invasive disease following neoadjuvant taxane-based chemotherapy and HER2-targeted therapy.
The decision marks the first European Union approval of trastuzumab deruxtecan in a curative-intent early breast cancer setting, extending the use of an antibody–drug conjugate (ADC) already established in the treatment of advanced cancers.
The European decision follows China’s approval of trastuzumab deruxtecan for the same adjuvant setting earlier in October 2026. As OncoDaily previously reported, China’s National Medical Products Administration (NMPA) approved the treatment on October 8, based on the same DESTINY-Breast05 findings, highlighting the expanding global regulatory recognition of this approach in HER2-positive early breast cancer.
Why Residual Disease After Surgery Matters
HER2-positive breast cancer accounts for approximately 20% of breast cancer diagnoses. Although HER2-targeted therapies have significantly improved outcomes, patients whose tumors do not achieve a pathologic complete response following neoadjuvant treatment remain at increased risk of recurrence.
For these patients, the postoperative pathology report becomes particularly important. The presence of residual invasive cancer indicates that some tumor cells survived preoperative therapy, suggesting a need for additional postoperative treatment.
For years, trastuzumab emtansine has been the standard approach in this setting, following the landmark KATHERINE trial. That study demonstrated that switching to T-DM1 after surgery improved invasive disease-free survival and, with longer follow-up, overall survival compared with continuing trastuzumab.
Yet recurrence remained a concern.
DESTINY-Breast05 was designed to answer a clinically important question: Could another antibody–drug conjugate provide even better protection against recurrence in patients whose cancer has already demonstrated resistance to initial treatment?
DESTINY-Breast05: What Did the Trial Show?
The global, randomized, open-label Phase 3 DESTINY-Breast05 trial enrolled 1,635 patients with HER2-positive early breast cancer, residual invasive disease after neoadjuvant treatment, and a high risk of recurrence.
Participants were assigned to receive either trastuzumab deruxtecan (818 patients) or trastuzumab emtansine (817 patients).
High-risk disease was defined by inoperable cancer at initial presentation or pathologically positive axillary lymph nodes following neoadjuvant therapy.
At a median follow-up of approximately 30 months, the results showed a clinically meaningful improvement with trastuzumab deruxtecan.
The three-year invasive disease-free survival rate was 92.4% with trastuzumab deruxtecan compared with 83.7% with T-DM1, representing an absolute difference of 8.7 percentage points.
Invasive disease recurrence or death occurred in 51 patients (6.2%) receiving trastuzumab deruxtecan, compared with 102 patients (12.5%) receiving T-DM1.
The hazard ratio was 0.47 (95% CI, 0.34–0.66; p<0.0001), corresponding to a 53% relative reduction in the risk of an invasive disease event or death.
The benefit was also reflected in disease-free survival, which includes additional events such as noninvasive breast cancer and second primary cancers. At three years, disease-free survival was 92.3% with trastuzumab deruxtecan and 83.5% with T-DM1.
The findings were first presented at the ESMO Congress 2025 and subsequently published in The New England Journal of Medicine (DOI: 10.1056/NEJMoa251466).
Read the latest updates on DESTINY-Breast05 from ESMO 2026.
Moving Antibody–Drug Conjugates Earlier in Breast Cancer Treatment
The importance of this approval extends beyond the comparison between two treatments.
Trastuzumab deruxtecan is a HER2-directed antibody–drug conjugate that combines a monoclonal antibody targeting HER2 with a topoisomerase I inhibitor payload. The antibody helps deliver the cytotoxic drug to HER2-expressing tumor cells.
The treatment has already demonstrated substantial clinical activity across several advanced and metastatic cancer settings. Its movement into early breast cancer reflects a broader shift in oncology: evaluating therapies with established activity in advanced disease earlier in the treatment pathway, where preventing recurrence may be possible.
For patients with residual invasive disease, postoperative treatment is particularly important because it offers an opportunity to target cancer cells that may remain elsewhere in the body, even after the primary tumor has been surgically removed.
The DESTINY-Breast05 results suggest that trastuzumab deruxtecan can improve disease control during this period.
However, the current findings should not be interpreted as proof of improved overall survival or cure rates. Longer follow-up will be necessary to determine whether the reduction in recurrence translates into a durable survival advantage.
Efficacy Comes With an Important Safety Consideration
Despite the encouraging efficacy findings, the safety profile of trastuzumab deruxtecan remains an essential consideration, particularly when treating patients with curative intent.
The trial identified gastrointestinal and hematologic adverse events, including nausea, vomiting, constipation, and neutropenia.
Of particular concern was drug-related interstitial lung disease (ILD), a recognized adverse effect of trastuzumab deruxtecan.
In DESTINY-Breast05, adjudicated drug-related ILD occurred in 9.6% of patients receiving trastuzumab deruxtecan compared with 1.6% receiving T-DM1. Two patients in the trastuzumab deruxtecan group died following ILD.
Although no new safety signals were identified, these findings emphasize the importance of appropriate patient selection, early recognition of pulmonary symptoms, and careful monitoring throughout treatment.
In the adjuvant setting, where many patients may already be disease-free after surgery, balancing the potential reduction in recurrence against treatment-related toxicity is especially important.
What the Approval Means for Clinical Practice
The European Commission’s decision follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).
Sibylle Loibl, MD, PhD, of the German Breast Group and Goethe University Medicine Frankfurt, and lead investigator of DESTINY-Breast05, described the approval as a development that “has the potential to change how we treat eligible patients in this setting.”
The approval also adds to the expanding role of trastuzumab deruxtecan across the breast cancer treatment continuum, from advanced disease to earlier stages where the therapeutic objective is long-term disease control and cure.
However, the new indication does not mean that every patient with residual HER2-positive disease will necessarily receive trastuzumab deruxtecan. The DESTINY-Breast05 population was specifically selected for a high risk of recurrence, and individual treatment decisions will need to account for disease characteristics, potential toxicities and patient preferences.
Access will also depend on national reimbursement and implementation decisions across European healthcare systems.
A New Chapter in Post-Neoadjuvant Breast Cancer Care
The approval of trastuzumab deruxtecan represents an important development in the management of HER2-positive early breast cancer.
For patients who do not achieve a complete response to neoadjuvant treatment, the period after surgery has long represented both a clinical challenge and an opportunity to improve outcomes.
DESTINY-Breast05 provides evidence that intensifying postoperative treatment with a more effective antibody–drug conjugate can substantially reduce the risk of invasive disease recurrence or death compared with the established standard.
The next questions will concern long-term survival, safety and which patients derive the greatest benefit.
For now, the European approval reinforces an increasingly important principle in breast cancer care: the treatment response before surgery can help guide what happens afterward, and residual disease does not have to mean accepting the same risk of recurrence.
