Wilmington, Del. — A combination of ENHERTU® (fam-trastuzumab deruxtecan-nxki) and pertuzumab has significantly improved outcomes for patients with HER2-positive metastatic breast cancer, according to new Phase III clinical trial data from the DESTINY-Breast09 study. The results were presented during a late-breaking oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
The trial demonstrated that the ENHERTU-based combination reduced the risk of disease progression or death by 44% compared to the current standard of care regimen—taxane, trastuzumab, and pertuzumab (THP). Patients treated with ENHERTU and pertuzumab achieved a median progression-free survival (PFS) of 40.7 months, significantly longer than the 26.9 months observed with THP, as assessed by blinded independent central review.
These findings represent the first meaningful improvement in first-line treatment outcomes for this patient population in over a decade. The benefit of the ENHERTU-pertuzumab combination was consistent across key subgroups, including hormone receptor status, PIK3CA mutation, and whether the disease was de novo or recurrent.
According to investigator assessments, the median PFS was 40.7 months for ENHERTU plus pertuzumab compared to 20.7 months with THP. The objective response rate was also higher—85.1% with ENHERTU and pertuzumab versus 78.6% with THP, with 58 complete responses reported in the ENHERTU group versus 33 in the comparator arm. The median duration of response exceeded three years for the ENHERTU combination.
While overall survival data are not yet mature, early analysis showed a trend favoring ENHERTU and pertuzumab over the standard THP regimen.
Dr. Sara Tolaney, principal investigator and Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, said the results offer promising news for patients. “These data show that trastuzumab deruxtecan combined with pertuzumab could become a new first-line standard of care, offering patients a longer period of disease control.”
Executives from both AstraZeneca and Daiichi Sankyo, co-developers of ENHERTU, emphasized the importance of these findings. AstraZeneca’s Susan Galbraith said the results highlight the benefit of initiating strong therapy at the time of metastatic diagnosis, especially since a significant number of patients do not receive further treatment after their first-line therapy. Daiichi Sankyo’s Ken Takeshita added that the results mark a breakthrough, offering improved outcomes for a broader population of patients with HER2-positive disease.
The DESTINY-Breast09 trial represents a potential shift in the treatment landscape, establishing a new benchmark in first-line therapy for HER2-positive metastatic breast cancer.
