Positive high-level results from the DESTINY-Breast11 Phase III 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 analysis; however, EFS data showed an early positive trend favouring Enhertu followed by THP compared to standard of care. The trial will continue to follow EFS.

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 involves 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.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “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. 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.”

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “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. 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."

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 enrolment in a third arm of the trial evaluating Enhertu alone was closed after a previous interim efficacy assessment of the trial arms. 

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

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Enhertu has demonstrated improved outcomes in six Phase III breast cancer trials across different subtypes and stages of disease, including the recently announced DESTINY-Breast09 Phase III trial in the 1st-line HER2-positive metastatic setting. Enhertu is also being studied in several ongoing breast cancer trials including the DESTINY-Breast05 Phase III trial which is evaluating Enhertu in the high-risk adjuvant early HER2-positive setting.