Enhertu extended progression-free survival to 13.2 months compared to 8.1 months with chemotherapy in patients with unresectable or metastatic hormone receptor–positive, HER2-low or HER2-ultralow metastatic breast cancer, according to a recent press release.
Enhertu (fam-trastuzumab deruxtecan-nxki) has received U.S. Food and Drug Administration approval as the first HER2-directed therapy for unresectable or metastatic hormone receptor (HR)-positive breast cancer, specifically targeting two distinct subgroups, HER2-low (IHC 1+ or IHC 2+/ISH-) and HER2-ultralow (IHC 0 with membrane staining), following progression on one or more endocrine therapies. This decision was based on results from the phase III DESTINY-Breast06 trial, published in The New England Journal of Medicine and presented at the 2024 American Society of Clinical Oncology Annual Meeting.
Led by Aditya Bardia, MD, MPH, of UCLA Health Jonsson Comprehensive Cancer Center, the trial enrolled 866 patients globally, including 713 with HER2-low and 153 with HER2-ultralow metastatic breast cancer. Patients received trastuzumab deruxtecan at 5.4 mg/kg or chemotherapy (capecitabine, paclitaxel, or nab-paclitaxel) as determined by investigators. Eligible participants' disease had progressed following at least two lines of endocrine therapy or one line combined with a CDK4/6 inhibitor. HER2 status was confirmed through central laboratory analysis of tumor samples obtained at initial metastatic diagnosis or later.
The trial demonstrated that trastuzumab deruxtecan significantly prolonged progression-free survival (PFS) compared with chemotherapy, with a median PFS of 13.2 months versus 8.1 months (hazard ratio = 0.64; 95% confidence interval = 0.54–0.76; P <0.0001). In the overall trial population, the objective response rate was 62.6% for trastuzumab deruxtecan compared with 34.4% for chemotherapy. Exploratory analyses showed consistent efficacy between HER2-low and HER2-ultralow patient subgroups.
Approximately 85% to 90% of HR-positive, HER2-negative metastatic breast cancers were identified as HER2-low or HER2-ultralow based on central laboratory testing, and nearly two-thirds of patients initially classified as IHC 0 were reclassified into these actionable categories.
The safety profile of trastuzumab deruxtecan was consistent with prior studies, with no new safety concerns reported.
Enhertu may redefine treatment paradigms for HR-positive metastatic breast cancer by introducing a targeted HER2-directed therapy for patients with HER2-low or HER2-ultralow disease, providing a new standard of care for those with limited therapeutic options after endocrine therapy. Researchers highlighted the importance of accurate HER2 testing to identify eligible patients.