Datroway Gains Landmark U.S. Approval for First-Line Treatment of Metastatic Triple-Negative Breast Cancer
In a major advancement for breast cancer treatment, Daiichi Sankyo and AstraZeneca have announced that the U.S. Food and Drug Administration (FDA) has approved Datroway® (datopotamab deruxtecan-dlnk) for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not eligible for PD-1/PD-L1 inhibitor therapy. The approval marks a significant milestone for patients with one of the most aggressive and difficult-to-treat forms of breast cancer, many of whom previously had limited treatment options beyond traditional chemotherapy.
Datroway is a next-generation TROP2-directed DXd antibody drug conjugate (ADC) developed by Daiichi Sankyo and AstraZeneca. The therapy combines a monoclonal antibody that targets TROP2 — a protein highly expressed in many cancers — with a potent chemotherapy payload designed to selectively attack tumor cells while minimizing damage to healthy tissue. The innovative design of the drug aims to improve efficacy and patient outcomes compared to conventional chemotherapy treatments.
The FDA approval was granted following a Priority Review based on positive results from the phase 3 TROPION-Breast02 clinical trial. Findings from the study were presented during the 2025 European Society for Medical Oncology Congress and later published in Annals of Oncology. The trial demonstrated that Datroway significantly improved survival outcomes in patients with metastatic TNBC who were not suitable candidates for immunotherapy.
One of the most notable outcomes from the study was the improvement in overall survival (OS). Patients treated with Datroway achieved a median overall survival of 23.7 months compared with 18.7 months for patients who received investigator’s choice chemotherapy. This represented a clinically meaningful 5.0-month improvement and a 21% reduction in the risk of death. Researchers described the results as statistically significant and highly encouraging for a patient population that historically faces poor outcomes.
The therapy also demonstrated a strong progression-free survival (PFS) benefit. Datroway reduced the risk of disease progression or death by 43% compared with chemotherapy. Median progression-free survival reached 10.8 months for patients treated with Datroway, nearly double the 5.6 months observed in the chemotherapy arm of the study. These findings suggest that the drug may help patients maintain disease control for substantially longer periods.
In addition to extending survival, Datroway produced significantly higher response rates. The objective response rate (ORR) in the trial was 64% among patients receiving Datroway, compared with 30% for those receiving chemotherapy. The higher response rate indicates that more patients experienced measurable tumor shrinkage with the ADC therapy than with standard chemotherapy regimens.
Experts involved in the trial highlighted the importance of the approval for patients with metastatic triple-negative breast cancer. Tiffany A. Traina, MD, FASCO, Section Head of the Triple Negative Breast Cancer Clinical Research Program at Memorial Sloan Kettering Cancer Center and an investigator in the TROPION-Breast02 trial, emphasized that Datroway is the first and only therapy to demonstrate a significant overall survival advantage over chemotherapy in the first-line setting for patients unable to receive immunotherapy.
According to Dr. Traina, the approval delivers a much-needed treatment option for patients who previously faced limited therapeutic choices. Triple-negative breast cancer is widely recognized as one of the most challenging forms of breast cancer because it lacks the hormone receptors and HER2 expression targeted by many existing therapies. As a result, treatment options have traditionally been limited, especially for patients who cannot receive immune checkpoint inhibitors.
Patient advocacy groups also welcomed the FDA’s decision. Arlene Brothers, Executive Director of the Triple Negative Breast Cancer Foundation, noted that approximately seven out of ten patients with metastatic TNBC who are not candidates for immunotherapy have historically depended on chemotherapy as their only frontline treatment option. She described the approval of Datroway as a transformative moment that introduces a new standard of care beyond conventional chemotherapy.
Safety data from the TROPION-Breast02 trial showed that Datroway had a manageable and generally consistent safety profile. The evaluation included 319 patients with TNBC who received the therapy at a dose of 6 mg/kg. The most common side effects included stomatitis, nausea, alopecia, fatigue, constipation, dry eye, keratitis, vomiting, musculoskeletal pain, and various laboratory abnormalities such as decreased blood counts and elevated liver enzymes.
Serious adverse reactions occurred in 17% of patients receiving Datroway. The most commonly reported serious side effects included pneumonia, vomiting, COVID-19 infection, and anemia. Investigators also reported one fatal case related to interstitial lung disease/pneumonitis, a known risk associated with some antibody drug conjugates. Healthcare providers are expected to monitor patients closely for respiratory symptoms and other potential complications during treatment.
Daiichi Sankyo executives described the approval as a landmark achievement for the company and for the broader field of ADC therapies. Ken Keller, Global Head of Oncology Business and President and CEO of Daiichi Sankyo, Inc., stated that Datroway is the first approved antibody drug conjugate to demonstrate a median overall survival of two years in the first-line metastatic setting of triple-negative breast cancer. He added that the therapy has the potential to reshape the treatment landscape for these patients.
Keller also noted that Datroway is now approved for three indications in the United States, including two breast cancer indications, underscoring the growing role of the therapy across multiple tumor types.
AstraZeneca executives echoed similar optimism about the drug’s future impact. Dave Fredrickson, Executive Vice President of the Oncology Hematology Business Unit at AstraZeneca, said metastatic triple-negative breast cancer remains extremely difficult to treat and that patients urgently need more durable and effective therapies. He emphasized that the approval broadens access to an important new treatment option for patients who are unable to receive immunotherapy and supports the companies’ ongoing efforts to evaluate Datroway across different cancers and treatment settings.
The FDA review of Datroway was conducted under Project Orbis, an international initiative that enables concurrent review of promising oncology therapies among global health authorities. Through the program, regulatory reviews are currently ongoing in countries including Australia, Canada, Singapore, and Switzerland. Additional applications are also under review in the European Union, China, and Japan.
The positive clinical results have already influenced treatment guidelines. Based on findings from the TROPION-Breast02 study, Datroway has been added to the NCCN Clinical Practice Guidelines in Oncology as a Category 1 Preferred first-line treatment option for patients with metastatic TNBC who are not candidates for immunotherapy. The inclusion in the NCCN Guidelines further reinforces the therapy’s importance and may accelerate adoption in clinical practice across the United States.
To support patient access, Daiichi Sankyo and AstraZeneca announced programs to help eligible patients obtain treatment and financial assistance. Support services for healthcare providers and patients are available through the Datroway4U program, which offers reimbursement guidance, patient assistance, and distribution support.
The approval of Datroway represents a breakthrough in the evolving field of antibody drug conjugates and offers renewed hope for patients facing metastatic triple-negative breast cancer. By significantly improving survival outcomes and providing an alternative to chemotherapy, the therapy may redefine frontline treatment standards for a patient population that has long needed more effective options.
About TROPION-Breast02
TROPION-Breast02 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and safety of Datroway versus the 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 tumors did not express PD-L1 as well as patients with PD-L1-expressing tumors who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrollment 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 PFS as assessed by BICR and OS. Secondary endpoints include PFS as assessed by the investigator, ORR, duration of response, disease control rate, pharmacokinetics, and safety.
TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America, and South America. For more information, visit ClinicalTrials.gov.
About Triple Negative Breast Cancer
TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.2,3 In the U.S., an estimated 32,000 to 48,000 cases of TNBC were diagnosed in 2025.4,5 TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.6,7,8 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.6,9,10
While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three.6 Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat.6 For patients with metastatic disease with PD-L1-expressing tumors, the addition of immunotherapy to chemotherapy has improved outcomes in the first-line setting.11,12 However, for approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, before the approval of Datroway, chemotherapy was the only approved first-line treatment.13
TROP2 is a protein broadly expressed in several solid tumors, including TNBC.14 TROP2 is associated with increased tumor progression and poor survival in patients with breast cancer.15,16
About Datroway
Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Datroway is one of seven DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datroway is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to several topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Datroway (6 mg/kg) is approved in more than 40 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial.
Datroway (6 mg/kg) is approved in Brazil, Russia and the U.S. for the treatment of adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy, based on the results from the TROPION-Breast02 trial.
Datroway (6 mg/kg) is approved in Russia and the U.S. for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy, based on the results from TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial.
About the Datroway Clinical Development Program
A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of Datroway across multiple cancers, including NSCLC, TNBC and urothelial cancer. The program includes eight phase 3 trials in lung cancer, five phase 3 trials in breast cancer, and one phase 3 trial and one phase 2/3 trial in urothelial cancer evaluating Datroway as a monotherapy and in combination with other cancer treatments in various settings.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize Enhertu® in March 2019 and Datroway in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway.
