Trastuzumab deruxtecan has received a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) for the adjuvant treatment of certain patients with HER2-positive early breast cancer, based on results from the Phase 3 DESTINY-Breast05 trial.
The recommendation covers trastuzumab deruxtecan as monotherapy for adults with resected HER2-positive breast cancer who have residual invasive disease after neoadjuvant taxane-based and HER2-targeted treatment.
The CHMP opinion will now be reviewed by the European Commission, which has authority to grant marketing authorization across the European Union.
Trastuzumab deruxtecan, a HER2-directed antibody-drug conjugate developed by Daiichi Sankyo and AstraZeneca, is already approved for this adjuvant setting in several countries, including the United States, Canada, Brazil and India.
DESTINY-Breast05 Shows 53% Reduction in Risk of Invasive Disease Recurrence or Death
The CHMP recommendation is supported by findings from the Phase 3 DESTINY-Breast05 trial (NCT04622319), a global, randomized, open-label study comparing trastuzumab deruxtecan with trastuzumab emtansine in patients with high-risk HER2-positive early breast cancer who had residual invasive disease following neoadjuvant therapy.
The trial enrolled 1,635 patients across Asia, Europe, North America, Oceania and South America.
Trastuzumab deruxtecan reduced the risk of invasive disease recurrence or death by 53% compared with trastuzumab emtansine, the current adjuvant standard of care in this setting.
The hazard ratio for invasive disease-free survival was 0.47 (95% CI, 0.34–0.66; p<0.0001).
At three years, the invasive disease-free survival rate was:
- 92.4% with trastuzumab deruxtecan
- 83.7% with trastuzumab emtansine
Trastuzumab deruxtecan also reduced the risk of disease recurrence or death according to the disease-free survival endpoint by 53%, with three-year disease-free survival rates of 92.3% versus 83.5%, respectively.
The DESTINY-Breast05 findings were initially presented at the 2025 ESMO Congress and subsequently published in The New England Journal of Medicine.
Potential New Adjuvant Option in HER2-Positive Early Breast Cancer
Patients who have residual invasive HER2-positive disease after neoadjuvant therapy remain at increased risk of recurrence despite surgery and additional systemic treatment.
John Tsai, Global Head of R&D at Daiichi Sankyo, highlighted the substantially higher risk of recurrence faced by these patients and said the CHMP opinion supports the potential role of trastuzumab deruxtecan in the curative-intent setting.
Susan Galbraith, Executive Vice President, Oncology Haematology R&D at AstraZeneca, described the recommendation as an important step toward bringing trastuzumab deruxtecan into early-stage HER2-positive breast cancer treatment in Europe.
Safety Profile in DESTINY-Breast05
The overall safety profile of trastuzumab deruxtecan was consistent with its established safety profile, with no new safety signals identified.
The most frequently reported treatment-related adverse events included nausea, constipation, decreased neutrophil count and vomiting.
Interstitial lung disease or pneumonitis occurred in 9.6% of patients receiving trastuzumab deruxtecan. Most cases were grade 1 or 2, although two grade 5 events (0.2%) were reported in the trastuzumab deruxtecan arm.
If the European Commission grants approval, trastuzumab deruxtecan could provide a new adjuvant treatment option for patients with HER2-positive early breast cancer who remain at high risk of recurrence because of residual invasive disease after neoadjuvant therapy.
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