Positive topline results from the DESTINY-Breast11 phase 3 trial showed ENHERTU^® (trastuzumab deruxtecan) followed by paclitaxel, trastuzumab and pertuzumab (THP) demonstrated a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) rate versus standard of care (dose-dense doxorubicin and cyclophosphamide followed by THP [ddAC-THP]) when used in the neoadjuvant setting (before surgery) in patients with high-risk, locally advanced HER2 positive early-stage breast cancer. Pathologic complete response is defined as no evidence of invasive cancer cells in the removed breast tissue and lymph nodes following treatment.

The secondary endpoint of event-free survival (EFS) was not mature at the time of this analysis; however, EFS data showed an early positive trend favoring ENHERTU followed by THP compared to standard of care. The trial will continue to follow EFS.

ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Approximately one in three patients with early-stage breast cancer are considered high-risk, as they are more likely to experience disease recurrence and have a poor prognosis. Achieving pCR in early-stage HER2 positive breast cancer is associated with improved long-term outcomes. The current standard of care in many regions of the world in this neoadjuvant setting consists of combination chemotherapy regimens. These regimens often include anthracyclines, which can be challenging for patients to tolerate and may result in long-term cardiovascular side effects. Further, nearly half of patients who receive neoadjuvant treatment do not achieve pCR, reinforcing the need for new treatment options.

“There are still many patients with early-stage breast cancer who do not achieve a pathologic complete response with treatment in the neoadjuvant setting, increasing the risk of disease recurrence,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “These topline results from DESTINY-Breast11 demonstrate that ENHERTU followed by THP could offer patients with HER2 positive breast cancer a promising new treatment approach prior to surgery, setting more patients on a path towards a potential cure.”

“The clinically meaningful improvement in pathologic complete response and the safety data seen in DESTINY-Breast11 highlight the potential of ENHERTU to challenge the current standard of care in early-stage HER2 positive breast cancer,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “ENHERTU is already an important treatment option in the metastatic setting, and these data have the potential to allow this medicine to move into early stages of disease where cure is possible.”

ENHERTU followed by THP showed an improved safety profile compared to ddAC-THP. The safety profiles of ENHERTU and THP were consistent with the known profiles of each individual medicine with no new safety concerns identified. Rates of interstitial lung disease were similar across the ENHERTU followed by THP and the ddAC-THP arms as determined by an independent adjudication committee.

Following a recommendation by the Independent Data Monitoring Committee, patient enrollment in a third arm of the study evaluating ENHERTU alone was closed based on a previous interim efficacy assessment of the study arms.

Data from DESTINY-Breast11 will be presented at an upcoming medical meeting and shared with regulatory authorities.

ENHERTU has demonstrated improved outcomes in six phase 3 breast cancer trials across different subtypes and stages of disease, including the recently announced DESTINY-Breast09 trial in the first-line HER2 positive metastatic setting. ENHERTU is also being studied in several ongoing breast cancer trials, including the DESTINY-Breast05 phase 3 trial, which is evaluating ENHERTU in the high-risk adjuvant early HER2 positive setting.