DESTINY-Breast11 Phase III Trial: Enhertu Plus THP Before Surgery Demonstrates Significant & Meaningful Pathologic Complete Response In High-Risk HER2-Positive Early-Stage Breast Cancer

The DESTINY-Breast11 Phase III trial has yielded positive high-level results, showing that Enhertu (trastuzumab deruxtecan) followed by paclitaxel, trastuzumab, and pertuzumab (THP) significantly improved the pathologic complete response (pCR) rate compared to the standard of care (dose-dense doxorubicin and cyclophosphamide followed by THP \[ddAC-THP]) when used in the neoadjuvant setting (before surgery) for patients with high-risk, locally advanced HER2-positive early-stage breast cancer. pCR is defined as the absence of invasive cancer cells in the breast tissue and lymph nodes after treatment.

Although the secondary endpoint of event-free survival (EFS) was not fully mature at the time of analysis, early data showed a positive trend favoring Enhertu followed by THP over the standard treatment. The trial will continue to monitor EFS data. Around 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 has been linked to better long-term outcomes. Current neoadjuvant treatments often involve chemotherapy regimens, which include anthracyclines that can be difficult for patients to tolerate and may cause long-term cardiovascular side effects. 

Additionally, nearly half of patients receiving neoadjuvant treatment do not achieve pCR, highlighting the need for new treatment options. Enhertu followed by THP showed a more favorable safety profile compared to ddAC-THP. The safety profiles of Enhertu and THP were consistent with their known individual profiles, with no new safety concerns identified. Rates of interstitial lung disease were similar in both treatment arms, as confirmed by an independent adjudication committee.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, stated, “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, mentioned, “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.”

Following a recommendation from the Independent Data Monitoring Committee, patient enrollment in the third arm of the trial, which was evaluating Enhertu alone, was closed after an interim efficacy assessment. Data from the DESTINY-Breast11 trial will be presented at an upcoming medical conference and shared with regulatory authorities. Enhertu, a specifically engineered HER2-directed DXd antibody drug conjugate (ADC), was discovered by Daiichi Sankyo and is being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. 

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