AstraZeneca and Daiichi Sankyo's Datroway (datopotamab deruxtecan) has been approved in the US for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.
The approval follows Priority Review by the Food and Drug Administration (FDA) based on results from the TROPION-Breast02 Phase III trial which were presented at the 2025 European Society for Medical Oncology Congress and published in Annals of Oncology.
Tiffany A. Traina, MD, FASCO, Section Head, Triple-Negative Breast Cancer Clinical Research Programme, Memorial Sloan Kettering Cancer Centre and investigator for TROPION-Breast02, said: "Datopotamab deruxtecan is the first and only medicine to significantly prolong overall survival in the 1st-line setting compared to chemotherapy in patients with metastatic triple-negative breast cancer who are not candidates for immunotherapy. This approval will bring a much-needed treatment option for these patients."
Arlene Brothers, Executive Director, Triple Negative Breast Cancer Foundation, said: "For seven out of 10 patients with metastatic triple-negative breast cancer who are not candidates for immunotherapy, chemotherapy has remained the only treatment option. Today's approval of Datroway means that for the first time, these patients will have a new standard of care beyond traditional chemotherapy at the outset of their treatment."
Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: "Triple-negative breast cancer is notoriously difficult to treat. Patients with metastatic disease, especially those who are unable to receive immunotherapy, urgently need more effective, durable and tolerable treatment options, which extend survival. With today's approval, we are proud to bring Datroway to a broad population of advanced triple-negative breast cancer patients and we continue to study its promise as a mainstay treatment across tumours, stages and settings."
Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc., said: "As the first antibody drug conjugate to demonstrate a median overall survival of two years in the 1st-line metastatic setting of triple-negative breast cancer, Datroway has the potential to redefine the treatment landscape for these patients. With this approval, Datroway is now approved for three indications in the US, including two for breast cancer, underscoring its potential to play an important role across tumour types."
In the trial, Datroway demonstrated a statistically significant and clinically meaningful 5.0-month improvement in median overall survival (OS) (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.64-0.98; p=0.0290) and a 43% reduction in patients' risk of disease progression or death (HR 0.57; 95% CI 0.47-0.69; p<0.0001) compared to chemotherapy as 1st-line treatment in this patient population. Datroway was also associated with more robust treatment responses, including an objective response rate (ORR) of 64% compared to an ORR of 30% with chemotherapy.1
The safety profile of Datroway in TROPION-Breast02 was consistent with previous clinical trials of Datroway in breast cancer.
This application was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, reviews are ongoing in Australia, Canada, Singapore and Switzerland. This initiative is designed to bring effective cancer treatments to patients as early as possible. Additional reviews are underway in the EU, China and Japan.
Based on the results of TROPION-Breast02, datopotamab deruxtecan (Datroway) has been included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a Category 1 Preferred 1st-line treatment option for patients with metastatic TNBC who are not candidates for immunotherapy. See NCCN Guidelines® for detailed recommendations.2
Datroway is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
Notes
Triple-negative breast cancer
TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.3,4 In the US, an estimated 32,000 to 48,000 cases of TNBC were diagnosed in 2025, and approximately 11,000 patients with TNBC receive treatment in the 1st-line setting each year.5-7 TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.8-10 Metastatic TNBC is the most aggressive type of breast cancer and has one of the worst prognoses, with median OS of just 12 to 18 months and only about 15% of patients living five years following diagnosis.8,11,12
While some breast cancers may test positive for oestrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three.8 Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat.8 For patients with metastatic disease with PD-L1 expressing tumours, the addition of immunotherapy to chemotherapy has improved outcomes in the 1st-line setting.13,14 However, for approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, prior to the approval of Datroway, chemotherapy was the only approved 1st-line treatment.15
TROP2 is a protein broadly expressed in several solid tumours, including TNBC.16 TROP2 is associated with increased tumour progression and poor survival in patients with breast cancer.17,18
TROPION-Breast02
TROPION-Breast02 is a global, multicentre, randomised, open-label Phase III trial evaluating the efficacy and safety of Datroway versus investigator's choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included patients whose tumours did not express PD-L1 as well as patients with PD-L1 expressing tumours who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrolment included patients with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such as stable brain metastases.
The dual primary endpoints of TROPION-Breast02 are progression-free survival (PFS) as assessed by blinded independent central review and OS. Secondary endpoints include PFS as assessed by investigator, ORR, duration of response, disease control rate, pharmacokinetics and safety.
