FDA Approves Trastuzumab Deruxtecan for HR-Positive, HER2-Low/-Ultralow Breast Cancer

On January 27, 2025, the US Food and Drug Administration (FDA) approved trastuzumab deruxtecan for patients with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-low or HER2-ultralow unresectable or metastatic breast cancer who experienced disease progression on or after 1 or more prior lines of endocrine therapy in the metastatic setting. This approval was based on results from the phase 3 DESTINY-Breast 06 trial.

This multicenter, open-label trial enrolled 866 patients with HER2-low (n = 713) and HER2-ultralow (n = 153) unresectable or metastatic breast cancer who received 1 or more prior lines of endocrine-therapy and no prior lines of chemotherapy in the metastatic setting. Patients were randomized on a 1-to-1 basis to receive either trastuzumab deruxtecan or physician’s choice of chemotherapy. The primary end point was progression-free survival (PFS) among patients with HER2-low disease. A key secondary end point was safety.

At analysis, PFS was 13.2 months in the trastuzumab deruxtecan arm and 8.1 months in the chemotherapy arm (hazard ratio, 0.62; 95% confidence interval, 0.52 to 0.75; P < .001). Grade ≥3 adverse events occurred in 52.8% and 44.4% of patients, respectively. Adjudicated interstitial lung disease occurred in 49 patients, 11.3% of which were grade 5.

“Trastuzumab deruxtecan offers a potential new standard of care for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer following endocrine therapy,” stated Aditya Bardia, MD, MPH, University of California, Los Angeles, California, an investigator in the DESTINY-Breast06 trial.

The recommended dose of trastuzumab deruxtecan is 5.4 mg/kg.

Source:

Enhertu 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. Accessed on January 28, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-approved-in-us-for-breast-cancer-post-et.html

Bardia A, Hu X, Dent R, et al. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. N Engl. J Med. Published online: September 14, 2024. doi: 10.1056/NEJMoa2407086