AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan (Dato-DXd) has failed to achieve statistical significance in overall survival (OS) in the Phase III TROPION-Breast01 trial, according to recent reports. The trial evaluated Dato-DXd compared to investigator's choice of chemotherapy in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative breast cancer who had been previously treated with endocrine-based therapy and at least one systemic therapy. While the trial had previously met its dual primary endpoint of progression-free survival (PFS), the final OS analysis did not show a statistically significant improvement.
The TROPION-Breast01 trial enrolled over 700 patients across multiple continents. Patients had the option to receive subsequent treatment at the discretion of their physician following disease progression or discontinuation of datopotamab deruxtecan or chemotherapy. The dual primary endpoints of TROPION-Breast01 were PFS as assessed by blinded independent central review and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety.
Impact on Treatment Landscape
The advanced treatment landscape for metastatic HR-positive breast cancer has seen remarkable progress. Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, stated, "Based on the TROPION-Breast01 results, there is evidence of the clinical value of datopotamab deruxtecan in this setting." The company plans to continue discussions with regulatory authorities to determine the next steps for the drug's development in breast cancer.
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, noted that datopotamab deruxtecan had previously demonstrated a statistically significant PFS benefit in the TROPION-Breast01 trial, supported by multiple meaningful secondary measures including patient-reported outcomes.
Safety and Tolerability
The safety profile of datopotamab deruxtecan was consistent with previous analyses, showing lower rates of Grade 3 or higher treatment-related adverse events compared to chemotherapy. Rates of all-grade interstitial lung disease (ILD) remained low, with no new Grade 3 or higher ILD events observed.
Future Directions
Datopotamab deruxtecan is a TROP2-directed DXd antibody-drug conjugate (ADC) discovered by Daiichi Sankyo and co-developed by AstraZeneca and Daiichi Sankyo. The companies are also evaluating datopotamab deruxtecan as a standalone treatment and in combination with immunotherapy for patients with triple-negative or HR-low, HER2-negative breast cancers in the TROPION-Breast02, TROPION-Breast03, TROPION-Breast04, and TROPION-Breast05 Phase III trials. The data from the TROPION-Breast01 trial will be presented at an upcoming medical meeting and shared with regulatory authorities.
