Datroway (datopotamab deruxtecan), an antibody-drug conjugate targeting TROP2, has become the first therapy to demonstrate an overall survival benefit over chemotherapy as first-line treatment for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) who are ineligible for immunotherapy. These landmark results from the TROPION-Breast02 trial represent a potential paradigm shift for the 70% of TNBC patients currently limited to chemotherapy as standard of care, addressing an urgent unmet need in this population with the poorest prognosis among all breast cancer subtypes.
Study Design & Population
- Trial: Phase 3 TROPION-Breast02 study evaluating Datroway versus chemotherapy
- Patient Population: Adults with locally recurrent inoperable or metastatic triple-negative breast cancer for whom immunotherapy is not an option
- Treatment Setting: First-line therapy
- Primary Endpoints: Overall survival (OS) and progression-free survival (PFS)
- Key Demographics: TNBC accounts for 15% of breast cancer cases, diagnosed more frequently in younger women and disproportionately affects Black and Hispanic patients
Key Findings
- Dual Primary Endpoint Success: Datroway achieved statistically significant and clinically meaningful improvements in both overall survival and progression-free survival compared to chemotherapy
- Historical Context: First cancer drug to demonstrate OS benefit versus chemotherapy in this specific patient population
- Current Standard Outcomes: Median OS for metastatic TNBC patients is 12-18 months, with only 14% surviving five years post-diagnosis
- Complete numerical data from the trial has not yet been disclosed
Clinical Implications
- Practice-Changing Potential: Results could establish Datroway as the new standard of care for approximately 70% of TNBC patients ineligible for immunotherapy
- Addresses Critical Gap: Provides first meaningful alternative to chemotherapy for this high-risk population with historically poor outcomes
- Regulatory Timeline: AstraZeneca and Daiichi Sankyo plan immediate regulatory submissions globally to expedite patient access
- Expanded Development: Three additional phase 3 trials (TROPION-Breast01, -03, -04) are investigating Datroway plus Imfinzi (durvalumab) across other TNBC treatment settings
- Treatment Sequencing: May redefine first-line approach for immunotherapy-ineligible TNBC patients
Development Status & Next Steps
- Regulatory Filings: Companies preparing global submissions with regulators based on TROPION-Breast02 results
- Current Approvals: Datroway already FDA-approved for HR-positive/HER2-negative breast cancer (January 2025) and EGFR-mutated NSCLC (June 2025)
- Ongoing Trials: Three phase 3 studies evaluating Datroway + Imfinzi combinations in various TNBC settings
- Commercial Trajectory: Peak sales potential estimated at $5 billion annually; part of $6 billion AstraZeneca-Daiichi Sankyo collaboration
- Previous Setback: FDA filing withdrawn for second-line nonsquamous NSCLC (November 2024) following mixed phase 3 results
Drug Profile & Mechanism
- Mechanism: Antibody-drug conjugate (ADC) targeting TROP2 protein expressed on tumor cell surfaces across multiple cancer types
- Development Partners: Co-developed by AstraZeneca and Daiichi Sankyo under collaboration initiated with $1 billion upfront payment (2020)
- Related Asset: Second ADC from partnership following Enhertu (trastuzumab deruxtecan), which generated $3.75 billion in sales (2024)
