Today, AstraZeneca and Daiichi Sankyo reported detailed positive results from the Phase 3 clinical trial DESTINY-Breast09 at the American Society of Clinical Oncology (ASCO) Annual Meeting. The data showed that compared with standard treatment, the重磅 antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) combined with pertuzumab as a first-line treatment for HER2-positive metastatic breast cancer patients demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS).The median PFS for patients treated with Enhertu in combination with pertuzumab exceeded three years.According to the press release,This is the first clinical trial in over a decade to demonstrate efficacy improvement in the first-line treatment regimen for a broad population of patients with HER2-positive metastatic breast cancer.

DESTINY-Breast09 is a global, multicenter, randomized, open-label Phase 3 trial designed to evaluate the efficacy and safety of Enhertu (5.4 mg/kg) used alone or in combination with pertuzumab, compared to the standard treatment of taxane, trastuzumab, and pertuzumab (THP), as a first-line therapy for patients with HER2-positive metastatic breast cancer. A total of 1,157 patients were enrolled, with the primary endpoint being progression-free survival (PFS) assessed by blinded independent central review (BICR) in both the Enhertu monotherapy and Enhertu combination therapy groups. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), investigator-assessed PFS, time to second disease progression (PFS2), and safety.

At the pre-specified interim analysis, the median follow-up time was close to 2.5 years (29.2 months). As of the data cutoff date, a total of 302 patients (39.6%) were still receiving treatment, including 174 in the Enhertu combination therapy group and 128 in the active control group. The analysis showed,Compared with the active control group, Enhertu in combination with pertuzumab reduced the risk of disease progression or death by 44% (HR=0.56; 95% CI: 0.44-0.71; p<0.00001).According to BICR,The median PFS was 40.7 months in the Enhertu combination therapy group and 26.9 months in the active control group.This PFS benefit remained consistent across all subgroups, including factors such as primary or recurrent disease, hormone receptor status, and PIK3CA mutation status.

▲Summary of DESTINY-Breast09 Trial Results (Image Source: Reference [1])

The confirmed ORR in the Enhertu combination therapy group was 85.1%, compared to 78.6% in the active control group.In the Enhertu combination therapy group, there were 58 cases of complete response (CR), compared to 33 cases in the active control group.The median DOR in the Enhertu combination therapy group exceeded three years (39.2 months), compared to 26.4 months in the active control group.

At the time of interim analysis, OS data were not yet mature (maturity was 16% as of the data cutoff); however, interim OS data showed an early benefit trend with Enhertu combination therapy compared to the active control group (HR=0.84; 95% CI: 0.59-1.19).

Sara Tolaney, M.D., Chief of Breast Oncology at Dana-Farber Cancer Institute and the principal investigator of this trial, stated: "Patients with HER2-positive metastatic breast cancer typically experience disease progression around two years after receiving standard first-line treatment.DESTINY-Breast09 Study Results Show,The median progression-free survival with Enhertu in combination with pertuzumab exceeded three years, indicating that this combination regimen has the potential to become a new first-line standard treatment for this patient population.”

In the DESTINY-Breast09 trial, the safety profile of Enhertu in combination with pertuzumab was consistent with the known safety profiles of the individual drugs, and no new safety issues were identified.

Enhertu is an ADC therapy jointly developed by AstraZeneca and Daiichi Sankyo.It is designed using Daiichi Sankyo's proprietary DXd ADC technology platform, consisting of a humanized monoclonal antibody targeting HER2 linked to a topoisomerase I inhibitor payload via a cleavable tetrapeptide linker. Enhertu was first approved by the U.S. FDA in 2019 for the treatment of patients with unresectable or metastatic HER2-positive breast cancer.

References:

[1] Enhertu 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. Retrieved June 2, 2025 from https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-plus-pertuzumab-reduced-the-risk-of-disease-progression-or-death-vs-thp-as-1st-line-therapy-in-patients-with-her2-positive-metastatic-breast-cancer.html

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