New results from the DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan) demonstrated a higher progression-free survival (PFS) and objective response rate (ORR) in pre-specified patient subgroups compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo).
A similar PFS and ORR benefit was observed in exploratory analyses in patients defined by stable brain metastases, hormone receptor status, number of prior lines of therapy, prior pertuzumab treatment, or status of visceral metastasis. Results were presented in an oral presentation at the 2021 San Antonio Breast Cancer Symposium (SABCS).
In patients with stable brain metastases at baseline, treatment with Enhertu resulted in higher PFS compared to T-DM1 (PFS by blinded independent central review (BICR) hazard ratio [HR] 0.25; 95% confidence interval [CI] 0.13-0.45). Additionally, in this subgroup, Enhertu improved PFS to a median of 15 months versus 3 months for T-DM1.
Sara Hurvitz, MD, FACP, medical oncologist, professor of medicine, and director of the Breast Cancer Clinical Trials Program in the division of hematology-oncology at the David Geffen School of Medicine at UCLA, and medical director for the Clinical Research Unit at the UCLA Jonsson Comprehensive Cancer Center in Santa Monica, CA, said: “The main goals in the treatment of HER2-positive metastatic breast cancer, including those with stable brain metastases are to improve symptoms, stabilise or reduce the tumour size and improve overall survival. The higher progression-free survival seen in DESTINY-Breast03 in the subgroup of patients with stable brain metastases are encouraging, and underscores the excitement around another potential treatment option for patients who have experienced disease progression on currently available therapies.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “More treatment options are needed to delay progression and extend survival for patients with HER2-positive metastatic breast cancer who develop brain metastases. These additional analyses from DESTINY-Breast03 reinforce the potential of Enhertu with similar benefits in the different subgroups.”
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “These additional analyses from DESTINY-Breast03 continue to demonstrate the benefit of Enhertu compared to T-DM1 in patient subgroups, including 15-month progression-free survival in those with stable brain metastases, illustrating the potential of this treatment to become the new standard of care in patients with previously treated HER2-positive metastatic breast cancer. These data will support our ongoing conversations with global health authorities to realise our commitment to bring Enhertu to patients with previously treated HER2-positive breast cancer earlier in the metastatic setting.”
Between 30 to 50% of patients with HER2-positive metastatic breast cancer will develop brain metastases, and while increased availability of HER2 therapies has improved systemic disease control, prognosis following the development of brain metastases remains poor.1-5
Confirmed ORR for patients with stable brain metastases at baseline was 67.4% with Enhertu versus 20.5% with T-DM1. A retrospective, non-prespecified evaluation of intracranial response among patients with stable brain metastases who received scans at baseline provided preliminary evidence that treatment with Enhertu is associated with intracranial tumour response and reduction in Central Nervous System disease with 10 (27.8%) complete responses (CR) and 13 (36.1%) partial responses (PR) compared to one (2.8%) CR and 11 (30.6%) PRs in those treated with T-DM1.
Summary of DESTINY-Breast03 subgroup analyses
