FDA Grants Priority Review to Post-Neoadjuvant T-DXd for HER2+ Early Breast Cancer

The FDA has accepted and granted priority review to a supplemental biologics license application (sBLA) seeking the approval of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the treatment of patients with HER2-positive breast cancer who have residual invasive disease following neoadjuvant HER2-targeted treatment.¹

With priority review granted, the FDA set a Prescription Drug User Fee Act target action date of July 7, 2026.

Priority review for post-neoadjuvant T-DXd aligns with the breakthrough therapy designation for the treatment in December 2025; the sBLA and breakthrough designation were supported by data from the phase 3 DESTINY-Breast05 trial (NCT04622319), which were presented at the 2025 ESMO Congress.^2,3 Data, which were simultaneously published in the New England Journal of Medicine, showed that patients treated with T-DXd (n = 818) experienced a 53% reduction in the risk of disease progression or death compared with patients who received ado-trastuzumab emtansine (T-DM1; Kadcyla; n = 817; HR, 0.47; 95% CI, 0.34-0.66; P < .0001).

Moreover, 3-year invasive disease–free survival (IDFS) rates were 92.4% (95% CI, 89.7%-94.4%) for patients in the T-DXd arm compared with 83.7% (95% CI, 80.2%-86.7%) for those in the T-DM1 arm.

“For patients with residual invasive disease after neoadjuvant therapy, identifying additional treatments following surgery is critical to help further reduce the risk of recurrence and help prevent progression to metastatic disease,” Ken Takeshita, MD, global head of R&D for Daiichi Sankyo, stated in a news release.¹ “This priority review reinforces the potential of T-DXs to become a new standard of care for HER2-positive early breast cancer based on the results of DESTINY-Breast05.”

What was the design of DESTINY-Breast05?

The global, open-label, multicenter trial enrolled patients at least 18 years of age with T1-4, N0-3, M0 breast cancer that was HER2 positive, defined as immunohistochemistry 3+ and/or in situ hybridization positive.⁴ Patients needed to have residual invasive carcinoma in the breast and/or axillary lymph nodes after completing neoadjuvant systemic therapy comprising a taxane and HER2-directed therapy. Patients also needed to have an ECOG performance status of 1 or less, known hormone receptor status, and adequate organ function.

Patients in the T-DXd arm received 5.4 mg/kg intravenous (IV) doses of the treatment once every 3 weeks for 14 cycles. Conversely, patients in the T-DM1 arm received IV doses of the treatment at 3.6 mg/kg once every 3 weeks for up to 14 cycles.

The trial’s primary end point was IDFS, whereas disease-free survival (DFS), overall survival (OS), distant recurrence-free survival, safety, and brain-metastasis free interval served as secondary end points.

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

What was the additional data for T-DXd in HER2-positive early breast cancer?

DFS rates were also improved in the T-DXd arm, with a 3-year DFS rate of 92.3% (95% CI, 89.5%-94.3%) compared with 83.5% (95% CI, 79.9%-86.4%) for the T-DM1 arm. Furthermore, 3-year OS rates were also higher for T-DXd, with patients achieving a rate of 97.4% (95% CI, 95.8%-98.4%); patients in the T-DM1 arm achieved a rate of 95.7% (95% CI, 93.5%-97.2%).

Regarding safety, the most common treatment-emergent adverse effects (TEAEs) in the T-DXd arm were nausea (71.3%), constipation (32%), vomiting (31%), decreased neutrophil counts (31.6%) and fatigue (29.5%). In the T-DM1 arm, common TEAEs were nausea (29.3%), increased aspartate aminotransferase levels (50.2%), increased alanine aminotransferase levels (45.3%), decreased platelet counts (49.8%), and radiation pneumonitis and (27%).

“Patients benefited [from T-DXd] irrespective of age cohorts, region of accrual, hormone receptor status, disease status at presentation, post-therapy pathologic nodal status, and dual or single HER2-targeted therapy,” Charles E. Geyer Jr., MD, a professor of medicine and chief of the Division of Malignant Hematology and Medical Oncology at the University of Pittsburgh Medical Center Hillman Cancer Center in a presentation of the data at the conference.

References

1. Enhertu granted priority review in the U.S. as post-neoadjuvant treatment for patients with HER2 positive early breast cancer. News release. Daiichi Sankyo. March 9, 2026. Accessed March 9, 2026. https://www.biospace.com/press-releases/enhertu-granted-priority-review-in-the-u-s-as-post-neoadjuvant-treatment-for-patients-with-her2-positive-early-breast-cancer
2. Geyer CE, Park YH, Shao Z, et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): interim analysis of DESTINY-Breast05. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA1.
3. Lobil S, Park YH, Shao Z, et al. Trastuzumab deruxtecan in residual HER2-positive early breast cancer. N Engl J Med. 2026;394(9):845-857. doi:10.1056/NEJMoa2514661
4. 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. Updated May 9, 2025. Accessed March 9, 2026. https://clinicaltrials.gov/study/NCT04622319