FDA

Enhertu approved for HER2-low/ultralow metastatic breast cancer

January 30, 2025

FDA approved Enhertu (fam-trastuzumab deruxtecan-nxki) for the treatment of adults with unresectable or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH]-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on ≥1 endocrine therapies in the metastatic setting.

Efficacy

Approval of the new indication was based on data from the phase 3 DESTINY-Breast06 trial (NCT04494425) in which Enhertu demonstrated a 36% reduction in risk of disease progression or death compared with investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.54-0.76; p<0.0001) in the overall trial population of patients with chemotherapy-naïve HER2-low or HER2-ultralow metastatic breast cancer. A median progression-free survival (PFS) of 13.2 months was seen in patients randomized to Enhertu compared with 8.1 in the chemotherapy group. The confirmed objective response rate (ORR) in the overall trial population was 62.6% for Enhertu vs. 34.4% for chemotherapy. At the time of the analysis, data for overall survival were immature.

In an exploratory analysis of patients with HER2-ultralow expression, results were found to be consistent between patients with HER2-low expression and HER2-ultralow expression.

Safety

The most common adverse reactions (≥20%) in patients with HER2-low and ultra-low metastatic breast cancer were leukopenia, nausea, decreased Hgb, neutropenia, lymphopenia, fatigue, thrombocytopenia, increased AST, ALT, and alkaline phosphatase, vomiting, alopecia, constipation, hypokalemia, decreased appetite, diarrhea, and musculoskeletal pain.

Sources:

Enhertu® (fam-trastuzumab deruxtecan-nxki) approved in the US as first HER2-directed therapy for patients with HER2-low or HER2-ultralow metastatic breast cancer following disease progression after one or more endocrine therapies. AstraZeneca. 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-approved-in-us-for-breast-cancer-post-et.html

Enhertu. Package insert. AstraZeneca. Accessed January 29, 2025. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true

Bardia A, et al. (2024, September 14). N Engl J Med. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. https://pubmed.ncbi.nlm.nih.gov/39282896/