FDA Accepts sBLA for T-DXd Plus THP in HER2+ Breast Cancer

The US FDA has accepted the supplemental biologics license application (sBLA) for trastuzumab deruxtecan (T-DXd; Enhertu) followed by paclitaxel (Taxol), trastuzumab (Herceptin), and pertuzumab (Perjeta; THP) for the neoadjuvant treatment of adult patients with HER2-positive stage 2 or 3 breast cancer.¹

A Prescription Drug User Fee Act (PDUFA) target action date of May 18, 2026, has been set. Data from DESTINY-Breast11 will also be presented at the upcoming European Society for Medical Oncology (ESMO) Congress during a presidential symposium (abstract #291O).

What Data Support the sBLA of T-DXd?

The sBLA is supported by data from the phase 3 DESTINY-Breast11 study (NCT05113251). Here, T-DXd followed by THP yielded a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) and an improved safety profile compared with dose-dense doxorubicin and cyclophosphamide followed by THP. There was also an early positive trend in event-free survival (EFS) favoring the T-DXd arm.

“Achieving a pathologic complete response prior to surgery in HER2-positive early-stage breast cancer is critical to reducing the risk of disease recurrence and improving the potential for cure,” said Ken Takeshita, MD, global head of Research and Development at Daiichi Sankyo, in a press release. “If approved, [T-DXd] could change how patients with high-risk HER2-positive early-stage breast cancer are treated, and we look forward to working closely with the FDA to bring this innovative treatment regimen to patients in this setting.”

What is the DESTINY-Breast11 Trial?

DESTINY-Breast11 is a randomized, open-label, phase 3 study comparing T-DXd vs doxorubicin and cyclophosphamide followed by THP before surgery in patients with high-risk, HER2-positive, early-stage breast cancer.² A third arm evaluating T-DXd alone was initially included in the study; however, this arm was closed following recommendations from an independent committee.³

The primary end point is pCR, and secondary end points include EFS, invasive disease-free survival (IDFS), and overall survival.²

The study enrolled 927 patients across sites in Asia, Europe, North America, and South America.¹ To be eligible for enrollment, patients were required to be at least 18 years of age, have histologically documented HER2-positive early breast cancer, have an ECOG performance status of 0 or 1, and have adequate organ and bone marrow function.²

What Other Data on T-DXd Will Be Presented at ESMO?

Data from the phase 3 DESTINY-Breast05 trial (NCT04622319) will also be presented at the 2025 ESMO Congress (abstract LBA1).⁴ Here, T-DXd demonstrated a highly statistically significant and clinically meaningful improvement in IDFS compared with trastuzumab emtansine (T-DM1; Kadcyla) in patients with high-risk, HER2-positive early breast cancer following neoadjuvant therapy.

REFERENCES:

1. ENHERTU® Followed by THP Supplemental Biologics License Application Accepted in the U.S. for Patients with High-Risk HER2 Positive Early-Stage Breast Cancer Prior to Surgery. News release. Daiichi Sankyo. October 1, 2025. Accessed October 2, 2025. https://tinyurl.com/mcxmzzax

2. Trastuzumab deruxtecan (T-DXd) alone or in sequence with THP, versus standard treatment (ddAC-THP), in HER2-positive early breast cancer. ClinicalTrials.gov. Updated August 3, 2025. Accessed October 2, 2025. https://clinicaltrials.gov/study/NCT05113251

3. Enhertu followed by THP before surgery showed statistically significant and clinically meaningful improvement in pathologic complete response in patients with high-risk HER2-positive early-stage breast cancer in DESTINY-Breast11 phase III trial. News release. AstraZeneca. May 7, 2025. Accessed October 2, 2025. https://tinyurl.com/42u3y2y3

4. Enhertu demonstrated highly statistically significant and clinically meaningful improvement in invasive disease-free survival vs. T-DM1 in DESTINY-Breast05 Phase III trial in patients with high-risk early breast cancer following neoadjuvant therapy. News release. AstraZeneca. September 29, 2025. Accessed October 2, 2025. https://tinyurl.com/yfyz6jp7