Positive results from the DESTINY-Breast11 phase 3 trial showed ENHERTU (trastuzumab deruxtecan) followed by paclitaxel, trastuzumab and pertuzumab (THP) in the neoadjuvant setting (before surgery) demonstrated a statistically significant and clinically meaningful improvement in the pathologic complete response (pCR) rate when compared with dose-dense doxorubicin and cyclophosphamide followed by THP (ddAC-THP) 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. Results were presented (291O) alongside the results from the DESTINY-Breast05 (LBA1) phase 3 trial during Presidential Symposium I at the 2025 European Society for Medical Oncology (#ESMO25) Congress.
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).
Health Technology Insights: Prolink Names Vanessa Janus Chief Workforce Solutions Officer
In the trial, ENHERTU followed by THP resulted in a pCR rate of 67.3% compared to 56.3% with ddAC-THP, representing a pCR rate improvement of 11.2% (95% confidence interval [CI]: 4.0-18.3; p=0.003). Improvements in pCR rates were observed across both HR positive and HR negative subgroups. After surgery, 81.3% of patients who received neoadjuvant therapy in the ENHERTU followed by THP arm had no or minimal residual invasive cancer (Residual Cancer Burden [RCB] 0+I) detected in the resected breast or lymph node tissue compared to 69.1% of patients in the comparator arm.
The secondary endpoint of event-free survival (EFS) was not mature at the time of this analysis (4.5% maturity at data cut-off); however, an early analysis showed a trend favoring ENHERTU followed by THP versus ddAC-THP (HR=0.56; 95% CI: 0.26-1.17).
“For patients with early breast cancer who are at high risk of disease recurrence, using the most effective treatment option at the earliest opportunity is critical to prevent recurrence, optimize safety and improve the potential for cure,”said Nadia Harbeck, Director of Breast Center, Cancer Department of OB&GYN and CCC Munich, LMU University Hospital, Germany and Principal Investigator for the trial. “In the DESTINY-Breast11 trial, more than two-thirds of patients had a pathologic complete response with trastuzumab deruxtecan followed by THP, suggesting a potential new standard of care in the neoadjuvant setting for patients with high-risk, HER2 positive early breast cancer.”
Health Technology Insights: Pelage Pharmaceuticals Raises $120 Million Series B to Boost Hair Loss Treatments
The safety profile of ENHERTU followed by THP in DESTINY-Breast11 was consistent with the known profiles of each individual therapy with no new safety concerns identified. ENHERTU followed by THP showed a favorable safety profile compared to ddAC-THP with reduced rates of grade 3 or higher treatment emergent adverse events (TEAEs) (ENHERTU followed by THP=37.5%; ddAC-THP=55.8%), serious adverse events (AEs) (ENHERTU followed by THP=10.6%; ddAC-THP=20.2%), treatment interruptions (ENHERTU followed by THP=37.8%; ddAC-THP=54.5%) and left ventricular dysfunction (ENHERTU followed by THP=1.3%; ddAC-THP=6.1%). The most common grade 3 or higher TEAEs occurring in 5% or more of patients treated with ENHERTU followed by THP were neutropenia (13.8%), diarrhea (5.9%) and increased transaminases (5.0%). Rates of interstitial lung disease (ILD) or pneumonitis were low and similar between arms with ILD events occurring in 4.4% (n=14/320) of patients treated with ENHERTU followed by THP compared to 5.1% (n=16/312) in those treated with ddAC-THP. The majority of ILD or pneumonitis events were low grade (grade 1 or grade 2 [ENHERTU followed by THP=12; ddAC-THP=10]), with one grade 3 or grade 4 events in the ENHERTU followed by THP arm and five grade 3 or 4 events in the ddAC-THP arm. There was one grade 5 ILD event in each arm as determined by an independent adjudication committee.
“While achieving a pathologic complete response in HER2 positive early-stage breast cancer is critical for reducing disease recurrence and improving long-term prognosis, approximately half of patients still show evidence of residual disease following surgery with currently available neoadjuvant treatment options,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo.“The results from DESTINY-Breast11 show that treatment with ENHERTUfollowed by THP prior to surgery resulted in no evidence of residual invasive disease in two-thirds of patients, illustrating the first treatment regimen in more than a decade to significantly improve outcomes in the earliest treatment setting for HER2 positive breast cancer.”
“The goal of treatment in the early breast cancer setting is to provide patients with the best possible chance for cure while optimizing the tolerability of the treatment regimen,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “The impressive pathologic response rates and favorable safety profile seen with ENHERTU followed by THP in DESTINY-Breast11 have the potential to transform treatment in the neoadjuvant setting and underscore the importance of bringing ENHERTU into earlier stages of HER2 positive disease.”
Approximately half of patients in DESTINY-Breast11 had a primary clinical tumor stage of 0-2 (cT0-2; ENHERTU followed by THP=54.8%; ddAC-THP=58.8%) and nearly half had a primary clinical tumor stage of 3-4 (cT3-4; ENHERTU followed by THP=45.2%; ddAC-THP=41.3%). The majority of patients were node positive (ENHERTU followed by THP=89.4%; ddAC-THP=87.8%) and had an ECOG PS (Eastern Cooperative Oncology Group performance status)of 0 (ENHERTU followed by THP=86.6%; ddAC-THP=87.5%). Nearly all patients underwent surgery following neoadjuvant treatment (ENHERTU followed by THP=97.2%; ddAC-THP=93.8%). As of the data cut-off date of March 12, 2025, the median duration of follow-up was 24.3 months in the ENHERTU followed by THP arm and 23.6 months in the ddAC-THP arm.
Health Technology Insights: Micro Interventional Devices Gets FDA Nod for STTAR-US Trial
To participate in our interviews, please write to our HealthTech Media Room at sudipto@intentamplify.com
Source- businesswire
