AstraZeneca–Daiichi Sankyo’s ADC, Enhertu, Gets FDA Priority Review in Early Breast Cancer

FDA has granted priority review to a supplemental biologics license application (sBLA) for trastuzumab deruxtecan (brand name Enhertu), an antibody-drug conjugate (ADC), as a post-neoadjuvant treatment for adult patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer who have residual invasive disease after neoadjuvant HER2-targeted therapy. ¹

Under a joint development and commercialization agreement between AstraZeneca and Daiichi Sankyo, Daiichi Sankyo is responsible for manufacturing and supply of trastuzumab deruxtecan. The companies have partnered to expand the therapy’s clinical development across multiple tumor types and treatment settings.¹

The sBLA is supported by findings from the Phase III DESTINY-Breast05 trial, which compared trastuzumab deruxtecan with trastuzumab emtansine (T-DM1) in patients with HER2-positive early breast cancer who had residual invasive disease following neoadjuvant therapy and were considered at high risk of recurrence. With priority review, the Prescription Drug User Fee Act action date for FDA’s decision is expected in the third quarter of 2026.

Why is the post-neoadjuvant setting an important focus for HER2-positive breast cancer?

Approximately one in five breast cancers are classified as HER2-positive, a subtype often associated with aggressive disease biology. Neoadjuvant therapy administered before surgery can improve long-term outcomes, particularly when patients achieve a pathologic complete response. However, a substantial proportion of patients still have residual invasive disease after neoadjuvant therapy. Clinical estimates suggest that roughly half of patients with HER2-positive early breast cancer fall into this category, which is associated with an increased risk of recurrence.²

Even with additional treatment after surgery, some patients progress to metastatic disease, where long-term survival rates decline significantly compared with earlier-stage disease.

“While there has been significant progress in treating HER2-positive early breast cancer, managing patients at a higher risk of recurrence remains challenging,” said Susan Galbraith, executive vice president, Oncology Hematology R&D, AstraZeneca, in a company press release.¹ “With this priority review, we move closer to bringing Enhertu to the post-neoadjuvant setting, offering more patients the opportunity for sustained long-term outcomes and a potential path to cure.”

What evidence supports the regulatory submission?

The Phase III trial evaluated trastuzumab deruxtecan at a dose of 5.4 mg/kg compared with T-DM1 in patients with HER2-positive early breast cancer who had residual invasive disease in the breast or axillary lymph nodes after neoadjuvant therapy. Trial results demonstrated a statistically significant improvement in invasive disease-free survival. Trastuzumab deruxtecan reduced the risk of invasive disease recurrence or death by 53% compared with T-DM1, corresponding to a hazard ratio of 0.47.¹

Three-year invasive disease-free survival reached 92.4% in the trastuzumab deruxtecan arm compared with 83.7% for T-DM1. Improvements were consistent across prespecified patient subgroups, according to companies. Additional findings showed reductions in distant recurrence risk and brain metastases incidence compared with T-DM1.¹

How could this decision influence the evolving ADC landscape?

Trastuzumab deruxtecan was developed using Daiichi Sankyo’s DXd ADC technology platform, which links a HER2-targeted monoclonal antibody to a topoisomerase I inhibitor payload via a cleavable linker. The ADC is already approved in more than 90 countries for multiple metastatic breast cancer indications and other HER2-expressing tumors.

Regulatory submissions based on the DESTINY-Breast05 Phase III trial are also under review in the European Union and Japan. Additional studies are evaluating the ADC in earlier treatment lines and in combination regimens.

As ADC development expands into earlier disease settings, regulatory decisions in the post-neoadjuvant setting may influence how targeted payload delivery strategies are integrated into curative-intent breast cancer treatment pathways.³

References

1. AstraZeneca. Enhertu granted Priority Review in the US as post-neoadjuvant treatment for patients with HER2-positive early breast cancer. Press Release. March 9, 2026.
2. Hendrix N, Oestreicher N, Lalla D, et al. Residual Disease Burden After Neoadjuvant Therapy Among US Patients With High-Risk HER2-positive Early-Stage Breast Cancer: A Population Effectiveness Model. Clin Breast Cancer. 2022;22(8):781-791. doi: 10.1016/j.clbc.2022.08.012
3. Patel P, Giordano A, Giordano S, et al. Antibody-drug conjugates for treating early-stage breast cancer: current use, anticipated evolutions. npj Breast Cancer 2025;11:81. doi: 10.1038/s41523-025-00800-4