ENHERTU® (trastuzumab deruxtecan) has been approved in Japan for adult patients with hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH–) or HER2 ultralow (IHC 0 with membrane staining) unresectable or recurrent breast cancer.
Discovered by Daiichi Sankyo, ENHERTU is a specifically engineered HER2-directed DXd antibody-drug conjugate (ADC) developed and commercialized by Daiichi Sankyo in Japan.
Breast cancer remains the most common cancer among women in Japan, with about 92,000 new cases and 17,600 deaths reported in 2022. HR positive, HER2 negative is the most frequent subtype, accounting for roughly 70% of breast cancers. Despite being labeled HER2 negative, many tumors still show some HER2 expression.
The approval by Japan’s Ministry of Health, Labour and Welfare is supported by data from the phase 3 DESTINY-Breast06 trial, presented at ASCO 2024 and published in The New England Journal of Medicine.
In DESTINY-Breast06, ENHERTU reduced the risk of disease progression or death by 38% versus chemotherapy in chemotherapy-naïve patients with HR positive, HER2 low metastatic breast cancer. Median progression-free survival (PFS) was 13.2 months with ENHERTU compared to 8.1 months with chemotherapy. In the HER2 ultralow subgroup, ENHERTU showed a median PFS of 13.2 months versus 8.3 months with chemotherapy.
“ENHERTU continues to transform the treatment landscape, becoming the first HER2-directed medicine in Japan for HR positive, HER2 low or ultralow metastatic breast cancer,” said Yuki Abe, PhD, Head of R&D Division, Daiichi Sankyo. “This marks the fifth approval for ENHERTU in Japan within five years, expanding treatment options for patients with lower HER2 expression.”
The safety profile was consistent with prior studies. Common treatment-emergent adverse events (TEAEs) included nausea, fatigue, alopecia, decreased neutrophil count, elevated liver enzymes, anemia, and vomiting. Interstitial lung disease (ILD) occurred in 20% of Japanese patients, requiring close monitoring and collaboration with respiratory specialists. ENHERTU carries a boxed warning for ILD, and treatment should be discontinued if early signs appear.
ENHERTU’s efficacy and safety as neoadjuvant or adjuvant therapy for HR positive, HER2 low or ultralow breast cancer have not yet been established. Use is restricted to patients confirmed with low or ultralow HER2 expression through approved diagnostic tests performed by experienced pathologists.