Positive results from the pivotal TROPION-Breast01 Phase III trial showed that datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to investigator’s choice of chemotherapy in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy.
These data will be shared today in the first of two late-breaking presentations for datopotamab deruxtecan in a Presidential Symposium at the European Society for Medical Oncology (ESMO) 2023 Congress in Madrid, Spain (LBA11).
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.
In the dual primary endpoint analysis, datopotamab deruxtecan reduced the risk of disease progression or death by 37% compared to investigator’s choice of chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.52-0.76; p
For the dual primary endpoint of overall survival (OS), interim results numerically favoured datopotamab deruxtecan over chemotherapy (HR 0.84; 95% CI 0.62-1.14), however, results did not reach statistical significance at the time of this data cut-off. The trial is ongoing to assess OS.
Aditya Bardia, MD, MPH, Director of Breast Cancer Research, Mass General Cancer Center, Associate Professor of Medicine at Harvard Medical School and investigator in the trial, said: “Despite the initial benefit of endocrine therapy, most patients with HR-positive, HER2-low or negative metastatic breast cancer will eventually experience disease progression and require additional treatment with chemotherapy. In the TROPION-Breast01 trial, datopotamab deruxtecan reduced patients’ risk of disease progression or death by more than a third and overall had fewer treatment-related serious adverse events than standard chemotherapy, illustrating its potential to become a new standard of care in a treatment setting where there is a clinical unmet need.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “With these TROPION-Breast01 results, datopotamab deruxtecan has the potential to meaningfully improve treatment expectations for patients with HR-positive, HER2-low or negative metastatic breast cancer by offering them an effective and better tolerated treatment option after endocrine therapy and only one line of chemotherapy. We look forward to continuing discussions with regulatory authorities with the goal of bringing this TROP2-directed antibody drug conjugate to eligible patients as soon as possible.”
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “These statistically significant and clinically meaningful results from the TROPION-Breast01 trial support datopotamab deruxtecan as a new potential standard of care for patients with advanced HR-positive, HER2-low or negative breast cancer in the post-endocrine therapy setting. The results further validate the portability of Daiichi Sankyo’s DXd antibody drug conjugate technology to additional targets such as TROP2, and we look forward to potentially bringing our second antibody drug conjugate to patients with breast cancer.”
Datopotamab deruxtecan demonstrated a favourable safety profile over chemotherapy with no new safety concerns identified. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 21% and 45% of patients in the datopotamab deruxtecan and chemotherapy arms, respectively. The most common Grade 3 or higher TRAEs were neutropenia (1%, 31%), stomatitis (6%, 3%), fatigue (2%, 2%) and anaemia (1%, 2%). In the datopotamab deruxtecan arm, the all-grade interstitial lung disease (ILD) rate was low (3%) and the majority of events were low grade. There was one Grade 5 ILD event adjudicated as drug-related by an independent committee. The primary cause of death in this case was attributed to disease progression by the treating investigator.
Summary of TROPION-Breast01 Efficacy Results
