Enhertu (trastuzumab deruxtecan) followed by THP before surgery showed statistically clinically meaningful improvement in response in patients with high-risk HER2-positive early-stage breast cancer in DESTINY-Breast11 trial- Daiichi Sankyo + AstraZeneca

Positive topline 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.

DESTINY-Breast11 (NCT05113251)  is a global, multicenter, randomized, open-label, phase III  trial evaluating the efficacy and safety of neoadjuvant Enhertu  (5.4 mg/kg) monotherapy or Enhertu followed by THP (paclitaxel ,trastuzumab and pertuzumab) versus the standard of care regimen in patients with high-risk (lymph node  positive [N1-3] or primary tumor stage T3-4), locally advanced or inflammatory HER2 positive early-stage breast cancer. Patients were randomized 1:1:1 to receive either eight cycles of Enhertu  monotherapy; four cycles of Enhertu followed by four cycles of THP; or four cycles of ddAC (dose-dense doxorubicin and cyclophosphamide) followed by four cycles of THP. The primary endpoint of DESTINY-Breast11 is rate of pCR (absence of invasive disease in the breast and lymph nodes). Secondary endpoints include EFS, invasive disease-free survival, overall survival and safety. DESTINY-Breast11 enrolled 927 patients across multiple sites in Asia, Europe, North America and South America.

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 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.

"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 Dr. Ken Takeshita,  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 Dr. Susan Galbraith,  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.”