Datroway Improves Survival in First-Line Treatment of Metastatic Triple- Breast Cancer

The Phase III TROPION-Breast02 trial demonstrated that datopotamab deruxtecan (Datroway) achieved a statistically significant and clinically meaningful improvement in both overall and progression-free survival compared with chemotherapy in patients with metastatic triple-negative breast cancer. If approved, Datroway could redefine the first-line treatment landscape for this aggressive disease.

AstraZeneca and Daiichi Sankyo announced that Datroway (datopotamab deruxtecan) has demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) as a first-line therapy for patients with metastatic triple-negative breast cancer (TNBC) who are not candidates for immunotherapy. The Phase III TROPION-Breast02 trial also met its co-primary endpoint of progression-free survival (PFS), showing superiority to physician’s choice of chemotherapy.

A first for a difficult-to-treat population

Metastatic TNBC remains one of the most aggressive forms of breast cancer, with median overall survival typically limited to 12–18 months. Approximately 70% of patients are not eligible for immunotherapy, often due to lack of PD-L1 expression or comorbid conditions. Until now, chemotherapy has been the only first-line option for these patients.

Dr. Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, highlighted the historic nature of the results: “TROPION-Breast02 is the only trial ever to show an overall survival benefit in the first-line treatment of patients with metastatic TNBC for whom immunotherapy is not an option. We expect today’s results will mark an inflection point in the treatment of these patients.”

Strong efficacy backed by consistent safety

According to the topline data, Datroway outperformed chemotherapy across both OS and PFS endpoints, establishing itself as the first and only therapy to do so in this setting. While detailed data will be presented at an upcoming medical congress, AstraZeneca and Daiichi Sankyo reported that the safety profile was consistent with prior Datroway studies in breast cancer, with no new safety signals observed.

About the TROPION-Breast02 trial

TROPION-Breast02 is a global, multicenter, randomized Phase III study enrolling 644 patients with locally recurrent inoperable or metastatic TNBC who had not received prior therapy for metastatic disease and were not eligible for immunotherapy. Participants were randomized to receive Datroway or investigator’s choice of chemotherapy (including paclitaxel, nab-paclitaxel, capecitabine, carboplatin, or eribulin).

The dual primary endpoints were overall survival and progression-free survival as assessed by blinded independent review, with secondary endpoints including response rate, duration of response, disease control rate, and safety.

Dr. Ken Takeshita, Global Head of R&D at Daiichi Sankyo, emphasized the broader implications of these findings: “Datroway is the first antibody drug conjugate and the only therapy to significantly improve overall survival compared to chemotherapy in patients with metastatic TNBC for whom immunotherapy is not an option. These landmark results from TROPION-Breast02 strengthen our confidence in our ongoing clinical development programme for Datroway.”

A novel ADC built on TROP2 targeting

Datroway is a TROP2-directed antibody-drug conjugate (ADC) that leverages Daiichi Sankyo’s proprietary DXd technology. It couples a humanized anti-TROP2 IgG1 antibody to a potent topoisomerase I inhibitor payload (DXd) via a cleavable tetrapeptide linker. TROP2 is widely expressed in TNBC and is associated with tumor aggressiveness and poor prognosis, making it a rational therapeutic target.

The agent is already approved in over 35 countries for HR-positive, HER2-low or -negative metastatic breast cancer following results from the TROPION-Breast01 trial, and it holds accelerated approval in the U.S. for EGFR-mutated non-small cell lung cancer.

Expanding the clinical development footprint 

Beyond TROPION-Breast02, Datroway is under investigation in multiple Phase III studies across early and advanced breast cancer settings: 

• TROPION-Breast03: Datroway ± Imfinzi (durvalumab) in Stage I–III TNBC with residual disease after neoadjuvant therapy. 
• TROPION-Breast04: Neoadjuvant Datroway + Imfinzi in Stage II–III TNBC or HR-low/HER2-low disease. 
• TROPION-Breast05: First-line Datroway ± Imfinzi in metastatic TNBC with PD-L1 expression.