Daiichi Sankyo announced ENHERTU® (trastuzumab deruxtecan) has been approved in China for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer that has progressed on one or more endocrine therapies in the metastatic setting. ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). Breast cancer is the second most common cancer in women in China.1 Approximately 357,000 cases of breast cancer were diagnosed in China in 2022, with nearly 75,000 deaths.1 HR positive, HER2 negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers.
2 Despite being classified as HER2 negative, many of these tumors still carry some level of HER2 expression.3 The approval of ENHERTU by China's National Medical Products Administration (NMPA) is based on results from the DESTINY-Breast06 phase 3 trial presented at the 2024 American Society of Clinical Oncology (#ASCO24) Annual Meeting and published in The New England Journal of Medicine. In DESTINY-Breast06, ENHERTU demonstrated a 38% reduction in the risk of disease progression or death versus chemotherapy in patients with chemotherapy-naïve HR positive, HER2 low metastatic breast cancer (n=713; hazard ratio [HR] 0.62; 95% confidence interval [CI]: 0.52-0.75; p<0.0001) as assessed by blinded independent central review (BICR). Median progression-free survival (PFS) was 13.2 months (95% CI: 11.4- 15.2) in the ENHERTU arm compared to 8.1 months (95% CI: 7.0-9.0) in the chemotherapy arm.
Confirmed objective response rate (ORR) in the HER2 low population was 56.5% (95% CI: 51.2-61.7) with ENHERTU compared to 32.2% (95% CI: 27.4, 37.3) with chemotherapy. Median duration of response (DOR) was 14.1 months (95% CI: 11.8-15.9) with ENHERTU compared to 8.6 months (95% CI: 6.7-11.3) with chemotherapy. In the HER2 ultralow population (n=153; HR 0.78; 95% CI: 0.50-1.21), median PFS was 13.2 months (95% CI: 9.8-17.3) in patients treated with ENHERTU compared to 8.3 months (95% CI: 5.8-15.2) in those treated with chemotherapy.
Confirmed ORR was 61.8% (95% CI: 50.0, 72.8) with ENHERTU compared to 26.3% (95% CI: 16.9, 37.7) with chemotherapy. Median DOR was 14.3 months (95% CI: 9.2, 20.7) with ENHERTU compared to 14.1 months (95% CI: 5.9-not estimable) with chemotherapy. The safety profile of ENHERTU in DESTINY-Breast06 was consistent with previous clinical trials with no new safety concerns identified.
The most common grade 3 or grade 4 adverse reactions from a pooled safety population receiving at least one dose of ENHERTU (n=2,225) were neutropenia (18.0%), anemia (10.5%), fatigue (7.8%), leukopenia (6.0%), thrombocytopenia (5.4%), nausea (4.9%), lymphopenia (3.9%), hypokalemia (3.8%), increased transaminases (3.5%), diarrhea (2.5%), vomiting (2.4%), decreased appetite (1.8%), pneumonia (1.3%) and decreased ejection fraction (1.0%). Grade 5 adverse reactions occurred in 1.4% of patients, including interstitial lung disease (ILD; 1.0%). Discontinuation of treatment due to an adverse reaction occurred in 11.2% of patients.
The most frequent adverse reaction associated with permanent discontinuation was ILD (8.1%).
