Regulatory Milestone: ENHERTU/THP Regimen Gains FDA Review for High-Risk HER2+ Breast Cancer
The U.S. FDA has accepted a supplemental Biologics License Application for AstraZeneca (NASDAQ: AZN) and Daiichi Sankyo’s ENHERTU® followed by paclitaxel, trastuzumab, and pertuzumab (THP), setting a review date of May 18, 2026. The new combination targets high-risk, HER2-positive, early-stage breast cancer patients ahead of surgery, based on results from the landmark DESTINY-Breast11 trial—the first phase 3 study to show a benefit in this population using this specific antibody drug conjugate approach.
Phase 3 DESTINY-Breast11 Shows Significant Pathologic Complete Response (pCR) Improvement
The trial randomized 927 patients with high-risk, locally advanced HER2-positive breast cancer to one of three arms: ENHERTU alone, ENHERTU followed by THP, or standard dose-dense doxorubicin and cyclophosphamide plus THP (ddAC-THP). The regimen of ENHERTU followed by THP demonstrated both a statistically significant and clinically meaningful improvement in pathologic complete response rates—a critical metric linked to long-term disease outcomes—compared to the standard regimen.
Event-free survival (EFS) also trended favorably in the ENHERTU-THP group, suggesting patients may experience fewer recurrences or disease progressions following this regimen. Importantly, ENHERTU’s safety profile remained consistent, with adverse event rates comparable to current standards and no new safety signals emerging in this phase 3 context.
| Trial Arm | Key Regimen | Primary Endpoint | Notable Results |
|---|---|---|---|
| ENHERTU + THP | ENHERTU (4 cycles) ? THP (4 cycles) | pCR, EFS | Significant pCR improvement; Positive EFS trend |
| ddAC + THP (Standard) | ddAC (4 cycles) ? THP (4 cycles) | pCR, EFS | Reference for current care |
This Regimen Could Reshape High-Risk Early Breast Cancer Treatment
Roughly one in three early-stage breast cancer patients are considered high-risk, often due to lymph node involvement or larger tumors. Currently, about half do not achieve a complete response to standard neoadjuvant therapy, highlighting a major unmet need. By delivering higher rates of complete pathologic response with an improved safety profile, ENHERTU followed by THP could offer these patients better long-term outcomes and a greater chance of cure.
Dr. Susan Galbraith, AstraZeneca’s Oncology R&D leader, remarked that this regimen "highlights the opportunity for ENHERTU followed by THP to become an important new approach for patients with HER2 positive early breast cancer." If approved, this could change the clinical standard of care, expanding the established utility of ENHERTU from metastatic to early-stage disease settings.
Safety and Side Effect Profile Remain Within Expectations
Across phase 3 studies, the most common side effects reported with ENHERTU include low white blood cell count (up to 73%), nausea (up to 76%), decreased hemoglobin (up to 67%), and fatigue (up to 55%). More serious adverse reactions like interstitial lung disease and left ventricular dysfunction occur but remain relatively uncommon (with Grade 3 or higher ILD seen in under 1% of patients in breast cancer populations).
| Most Common Side Effects (≥20%) | ENHERTU Pooled Trials |
|---|---|
| Low white blood cell count | 73% |
| Nausea | 72% |
| Low hemoglobin | 67% |
| Neutropenia | 65% |
| Fatigue | 55% |
| Low platelet count | 48% |
| Vomiting | 38% |
The FDA continues to monitor long-term risks, especially interstitial lung disease and embryo-fetal toxicity, with guidelines for dose interruptions or discontinuation in more severe cases. (See the official product label for full details on safety monitoring.)
What’s Next: Awaiting Final FDA Decision and Additional Data at Major Medical Congresses
The FDA has set a target review date of May 18, 2026, under the Prescription Drug User Fee Act (PDUFA). Meanwhile, further results from the DESTINY-Breast11 and related trials will be shared at the European Society for Medical Oncology (ESMO) Congress in October 2025. Should the regimen receive approval, it could usher in a new era of neoadjuvant therapy for a subset of breast cancer patients at highest risk of recurrence.
Takeaway: ENHERTU’s Momentum Points Toward a Potential Paradigm Shift in Early-Stage Breast Cancer
This FDA application represents a potentially major advance in early-stage, high-risk, HER2-positive breast cancer, especially for patients unlikely to achieve cure with current therapies. Investors, oncologists, and patients will want to track the regulatory outcome and evolving clinical evidence over the coming year, as ENHERTU plus THP edges closer to redefining the front-line treatment landscape.
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