In the DESTINY-Breast09 study, Enhertu (fam-trastuzumab deruxtecan-nxki) plus pertuzumab reduced the risk of disease progression or death by 44% in patients with HER2-positive metastatic breast cancer.
Enhertu plus pertuzumab showed a 44% reduction in disease progression or death versus the current standard-of-care THP regimen.
The combination therapy achieved a median PFS of 40.7 months, setting a new potential first-line standard for HER2-positive metastatic breast cancer.
DESTINY-Breast09 highlights efficient trial execution across global sites, emphasizing the importance of well-structured multicenter design in oncology trials.
AstraZeneca and Daiichi Sankyo have shared positive data from the Phase III DESTINY-Breast09 clinical trial (NCT04784715) of Enhertu (fam-trastuzumab deruxtecan-nxki) plus pertuzumab as a first-line treatment for patients with HER2-positive metastatic breast cancer.1
The Enhertu-pertuzumab combination demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to a taxane, trastuzumab, and pertuzumab (THP) regimen. Detailed data from the DESTINY-Breast09 study were shared at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
Results from a prespecified interim analysis showed that Enhertu and pertuzumab reduced the risk of disease progression or death by 44% versus THP. The Enhertu-pertuzumab combination achieved a median PFS of 40.7 months, compared to 6.9 months for THP. The PFS benefit for Enhertu and pertuzumab was consistent across multiple patient subgroups including de novo or recurrent disease, hormone receptor status, and PIK3CA mutation status.
In a press release, Sara Tolaney, MD, MPH, chief of the division of breast oncology, Dana-Farber Cancer Institute and principal investigator in the trial, said: “Patients with HER2-positive metastatic breast cancer often experience disease progression around two years after initiating standard-of-care first-line treatment. With a median progression-free survival of more than three years, the DESTINY-Breast09 results show trastuzumab deruxtecan combined with pertuzumab has the potential to become a new first-line standard of care for these patients.”
The Enhertu-pertuzumab duo had a confirmed objective response rate (ORR) of 85.1% versus 78.6% for THP. There were 58 complete responses with Enhertu plus pertuzumab compared to 33 with THP. Enhertu plus pertuzumab demonstrated a median duration of response (DOR) of 39.2 months, while THP demonstrated 26.4 months.
According to AstraZeneca, overall survival (OS) data were not mature at the time of this analysis. However, the interim data show an early trend favoring the Enhertu-pertuzumab combination compared to THP.
The Phase III DESTINY-Breast09 trial is a global, multicenter, randomized, open-label study enrolling patients at multiple sites in Africa, Asia, Europe, North America, and South America. The study features arms for Enhertu as monotherapy, Enhertu plus pertuzumab, and THP. A total of 1,157 patients were randomized in a 1:1:1 ratio across the three arms.2
The study’s primary endpoint is PFS, plus key secondary endpoints including investigator-assessed PFS, OS, ORR, duration of response, investigator-assessed time to second progression or death, patient-reported tolerability, pharmacokinetics, and safety.
AstraZeneca initially shared news of Enhertu plus pertuzumab demonstrating a significant improvement in PFS in patients with HER2-positive metastatic breast cancer earlier in April.2
In a press release from the time, Susan Galbraith, executive vice president, oncology hematology R&D, AstraZeneca, said “This is the first trial in more than a decade to demonstrate superior efficacy across a broad HER2-positive metastatic breast cancer patient population compared to the current first-line standard of care. This is a significant milestone for patients and sets the foundation for Enhertu in combination with pertuzumab as an important treatment option in the first-line HER2-positive setting.”
Enhertu is also being evaluated in the Phase III DESTINY-Breast11 trial (NCT05113251) in patients with high-risk, locally advanced HER2-positive early-stage breast cancer. In May, AstraZeneca shared that Enhertu followed by standard HER2-targeted therapy demonstrated a significant improvement in pathologic complete response (pCR) rates compared to current standard-of-care chemotherapy.3
DESTINY-Breast11 randomized 927 patients 1:1:1 to receive either eight cycles of Enhertu monotherapy, four cycles of Enhertu and then four cycles of THP, or four cycles of dose-dense doxorubicin and cyclophosphamide followed by four cycles of THP. The trial’s primary endpoint is pCR, plus secondary endpoints including event-free survival, invasive disease-free survival, OS, and safety.
1. ENHERTU® (fam-trastuzumab deruxtecan-nxki) plus pertuzumab reduced the risk of disease progression or death by 44% vs. THP as 1st-line therapy in patients with HER2-positive metastatic breast cancer in DESTINY-Breast09 Phase III trial. News release. AstraZeneca. June 2, 2025. Accessed June 2, 2025. https://www.businesswire.com/news/home/20250602557687/en/ENHERTU-fam-trastuzumab-deruxtecan-nxki-plus-pertuzumab-reduced-the-risk-of-disease-progression-or-death-by-44-vs.-THP-as-1st-line-therapy-in-patients-with-HER2-positive-metastatic-breast-cancer-in-DESTINY-Breast09-Phase-III-trial
2. DESTINY-Breast09 Trial Shows Enhertu Plus Perjeta Significantly Improves Survival in HER2-Positive Metastatic Breast Cancer. Applied Clinical Trials. April 21, 2025. Accessed June 2, 2025. https://www.appliedclinicaltrialsonline.com/view/enhertu-perjeta-survival-her2-metastatic-breast-cancer
3. DESTINY-Breast11 Trial Shows Enhertu Plus THP Significantly Improves Response Rates in High-Risk HER2-Positive Early Breast Cancer. Applied Clinical Trials. May 7, 2025. Accessed June 2, 2025. https://www.appliedclinicaltrialsonline.com/view/destiny-breast11-enhertu-her2-positive-early-breast-cancer
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