TRASTUZUMAB deruxtecan combined with pertuzumab significantly delayed disease progression compared to standard care in patients with HER2-positive advanced breast cancer, according to initial findings from the DESTINY-Breast09 Phase III trial.
The study evaluated 1,157 patients with locally advanced or metastatic HER2-positive breast cancer who had not previously received chemotherapy or HER2-targeted therapy. Participants were randomized to receive trastuzumab deruxtecan with pertuzumab, trastuzumab deruxtecan with a placebo, or the standard first-line regimen of trastuzumab, pertuzumab, and a taxane (THP). The current analysis focused on data from the trastuzumab deruxtecan–pertuzumab and THP arms.
With a median follow-up of 29 months, the trastuzumab deruxtecan–pertuzumab combination reduced the risk of disease progression or death by 44% compared with THP. Median progression-free survival (PFS) was 40.7 months in the trastuzumab deruxtecan–pertuzumab group versus 26.9 months in the THP group. This benefit was observed across multiple patient subgroups, including those with de novo metastatic disease and hormone receptor–positive cancers.
At two years, approximately 70% of patients receiving the trastuzumab deruxtecan–pertuzumab combination remained progression-free, compared to 52% in the THP group. Objective response rates were also higher in the trastuzumab deruxtecan–pertuzumab arm, with 85% of patients experiencing tumor shrinkage or disappearance compared to 78.6% in the THP group. Complete responses were reported in 15% of patients in the experimental group, nearly double the rate seen with standard care.
Although overall survival data remain immature, early results suggest a favorable trend. Safety profiles were comparable between groups, though gastrointestinal side effects such as nausea and constipation were more frequent in the trastuzumab deruxtecan–treated cohort. Interstitial lung disease, a known risk of trastuzumab deruxtecan, occurred in 12% of patients; most cases were not severe.
These findings suggest trastuzumab deruxtecan with pertuzumab may represent a potential new option for first-line treatment in this patient population. Ongoing follow-up will clarify the overall survival benefit and long-term tolerability.
Reference:
American Society of Clinical Oncology (ASCO). Trastuzumab Deruxtecan With Pertuzumab May Delay Cancer Growth for Some Patients with HER2-Positive Advanced Breast Cancer. 2025. Available at: https://www.asco.org/about-asco/press-center/news-releases/trastuzumab-deruxtecan-pertuzumab-destiny-breast09. Last accessed: 18 June 2025.
