29 April 2024
Enhertu demonstrated statistically significant and clinically meaningful improvement in progression-free survival in HR-positive, HER2-low metastatic breast cancer following one or more lines of endocrine therapy in DESTINY-Breast06 Phase III trial
AstraZeneca and Daiichi Sankyo’s Enhertu also demonstrated a clinically meaningful progression-free survival improvement
in patients with HER2-ultralow expression
Positive high-level results from the DESTINY-Breast06 Phase III trial showed that Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard-of-care chemotherapy in the primary trial population of patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) metastatic breast cancer following one or more lines of endocrine therapy.
A statistically significant and clinically meaningful improvement in PFS was also observed in the overall trial population (patients with HER2-low and HER2-ultralow [defined as IHC 0 with membrane staining; IHC >0<1+] metastatic breast cancer). A prespecified subgroup analysis showed the clinically meaningful improvement was consistent between patients with HER2-low and HER2-ultralow expression.
Overall survival (OS) data were not mature at the time of the analysis; however, Enhertu showed an early trend towards an OS improvement versus standard-of-care chemotherapy in patients with HER2-low metastatic breast cancer and in the overall trial population. The trial will continue as planned to further assess OS and other secondary endpoints.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “DESTINY-Breast06 shows that Enhertu could become a new standard of care for patients with HER2-low and HER2-ultralow metastatic breast cancer following one or more lines of endocrine therapy. These data underscore the potential for treatment with Enhertu across the spectrum of HR-positive breast cancer, further redefining the treatment of metastatic breast cancer.”
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “The topline results from DESTINY-Breast06 highlight the importance of continuing to challenge current treatment paradigms and established breast cancer classifications to evolve how we treat patients with HR-positive, HER2-expressing metastatic breast cancer. Building on the practice-changing data seen in DESTINY-Breast04, these results reinforce the potential for use of Enhertu earlier in the treatment landscape and in an even broader patient population.”
Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
It is estimated that approximately 60-65% of HR-positive, HER2-negative breast cancers are HER2-low and potentially an additional 25% may be HER2-ultralow.1,2 Endocrine therapies are widely used in the early lines of treatment for HR-positive metastatic breast cancer; however after two lines of treatment, further efficacy from endocrine therapy is often limited.3 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.3-6
The safety profile of Enhertu was consistent with previous breast cancer clinical trials with no new safety signals identified.
The data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.