AstraZeneca, Daiichi Sankyo’s ENHERTU demonstrates improvement in PFS

Detailed results from the DESTINY-Breast06 Phase III trial showed that ENHERTU demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared to standard-of-care chemotherapy in patients with HR-positive, HER2-low metastatic breast cancer and the overall trial population following one or more lines of endocrine therapy. These results will be presented today as a late-breaking oral presentation during the 2024 American Society of Clinical Oncology Annual Meeting. ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. In the primary analysis of DESTINY-Breast06, results showed ENHERTU reduced the risk of disease progression or death by 38% by blinded independent central review versus chemotherapy in patients with HER2-low expression. Median PFS was 13.2 months in the ENHERTU arm compared to 8.1 months for chemotherapy. PFS results by BICR in the overall trial population were similar and showed ENHERTU achieved a 37% reduction in the risk of disease progression or death compared to chemotherapy, with a median PFS of 13.2 months with ENHERTU versus 8.1 months for chemotherapy. A prespecified exploratory analysis showed the clinically meaningful improvement in PFS was consistent between patients with HER2-low and HER2-ultralow expression. In patients with HER2-ultralow expression, ENHERTU reduced the risk of disease progression or death by 22% compared to chemotherapy with a median PFS of 13.2 months versus 8.3 months, respectively. In patients with HER2-low expression, confirmed objective response rate was 56.5% for ENHERTU versus 32.2% with chemotherapy. In the overall trial population, confirmed ORR was 57.3% for ENHERTU versus 31.2% with chemotherapy and in patients with HER2-ultralow expression the confirmed ORR was 61.8% versus 26.3%, respectively. Complete responses were seen in 13 patients from the ENHERTU arm, including nine patients with HER2-low expression. In the HER2-ultralow subgroup, four patients in the ENHERTU arm had complete responses. No complete responses were seen in the chemotherapy arm. Patients in the trial received a median of two prior lines of endocrine therapy in each treatment arm. In the overall trial population, 14.9% of patients in the ENHERTU arm and 19.2% of patients in the chemotherapy arm had received one prior line of endocrine therapy. No patients in the trial had received prior chemotherapy treatment in the metastatic setting. Median duration of follow-up was 18.2 months. As of the data cut-off of March 18, 2024, a total of 119 patients remained on treatment, 89 patients receiving ENHERTU and 30 receiving chemotherapy. The safety profile of ENHERTU was consistent with previous breast cancer clinical trials with no new safety concerns identified.