EU Approval Positions Datroway® as the Only TROP2-Targeted Therapy with Overall Survival Benefit in First-Line Metastatic TNBC
The European Commission (EC) has approved Datroway® (datopotamab deruxtecan) as a monotherapy for the first-line treatment of adults with unresectable or metastatic triple-negative breast cancer (TNBC) who are not eligible for PD-1/PD-L1 inhibitor therapy. The decision provides a significant new treatment option for a large group of patients with one of the most aggressive forms of breast cancer, where therapeutic choices have historically been limited and prognosis often remains poor.
Datroway is a TROP2-directed DXd antibody-drug conjugate (ADC) discovered by Daiichi Sankyo and is being jointly developed and commercialized with AstraZeneca. The approval marks another milestone in the expanding role of antibody-drug conjugates in oncology, particularly for difficult-to-treat cancers where conventional chemotherapy has been the primary treatment option for many years.
The European Commission’s decision follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) and is supported by compelling data from the pivotal Phase 3 TROPION-Breast02 clinical trial. The study demonstrated that Datroway significantly improved overall survival, progression-free survival, and tumor response rates compared with standard chemotherapy in patients with metastatic TNBC who were not candidates for immunotherapy.
Addressing a Critical Unmet Need in Triple-Negative Breast Cancer
Triple-negative breast cancer accounts for approximately 10% to 20% of all breast cancer diagnoses and is widely recognized as one of the most challenging breast cancer subtypes to treat. Unlike other forms of breast cancer, TNBC lacks expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2), eliminating several highly effective targeted treatment approaches.
Patients with metastatic TNBC often experience rapid disease progression and generally have poorer survival outcomes compared with other breast cancer subtypes. While immunotherapy has improved outcomes for selected patients, a substantial proportion of individuals are either ineligible or unlikely to benefit from PD-1/PD-L1 inhibitor treatment because of tumor biology or biomarker status.
For these patients, chemotherapy has remained the primary first-line treatment despite modest survival benefits and significant treatment-related toxicity.
The approval of Datroway introduces a targeted therapeutic option that offers improved clinical outcomes over conventional chemotherapy for this patient population.
Mechanism of Action
Datroway belongs to a rapidly growing class of cancer medicines known as antibody-drug conjugates (ADCs).
The therapy combines a monoclonal antibody that specifically recognizes TROP2, a protein highly expressed on many cancer cells, with Daiichi Sankyo’s proprietary DXd topoisomerase I inhibitor payload.
Once the antibody binds to TROP2 on the tumor cell surface, the ADC is internalized into the cancer cell, where the cytotoxic payload is released. This targeted approach delivers chemotherapy directly to tumor cells while limiting exposure to surrounding healthy tissues.
By selectively targeting cancer cells, antibody-drug conjugates seek to improve treatment efficacy while reducing some of the systemic toxicities commonly associated with conventional chemotherapy.
Phase 3 TROPION-Breast02 Trial
The European approval is primarily based on results from the global Phase 3 TROPION-Breast02 trial, which evaluated Datroway as first-line treatment in patients with unresectable or metastatic TNBC who had experienced early relapse following previous therapy and were not suitable candidates for PD-1/PD-L1 inhibitor treatment.
Results from the study were first presented during the 2025 European Society for Medical Oncology (ESMO) Congress before being published in the peer-reviewed journal Annals of Oncology.
The trial compared Datroway with investigator’s choice of standard chemotherapy.
Significant Improvement in Overall Survival
One of the study’s most important findings was the statistically significant improvement in overall survival (OS).
Patients receiving Datroway achieved a median overall survival of 23.7 months, compared with 18.7 months among patients treated with standard chemotherapy.
This represents a five-month improvement in median survival, with a hazard ratio of 0.79, indicating a meaningful reduction in the risk of death.
For patients living with metastatic TNBC, where survival gains have traditionally been limited, a five-month improvement represents a clinically important advancement.
Superior Progression-Free Survival
In addition to extending overall survival, Datroway significantly delayed disease progression.
The study demonstrated a 43% reduction in the risk of disease progression or death compared with chemotherapy, as assessed by blinded independent central review.
Median progression-free survival reached 10.8 months in the Datroway treatment group versus 5.6 months in the chemotherapy arm.
Doubling progression-free survival provides patients with substantially longer periods before disease worsening while potentially delaying the need for additional treatment.
Higher Tumor Response Rates
Datroway also demonstrated markedly stronger anti-tumor activity.
The objective response rate reached 62.5%, meaning nearly two-thirds of treated patients experienced measurable tumor shrinkage.
By comparison, only 29.3% of patients receiving chemotherapy achieved a similar response.
These findings suggest that Datroway not only prolongs survival but also produces more frequent and meaningful reductions in tumor burden.
Clinical Perspective
Dr. Giuseppe Curigliano, Director of the Early Drug Development Division at the European Institute of Oncology and Professor of Medical Oncology at the University of Milan, emphasized the significance of the approval for patients with metastatic triple-negative breast cancer.
He noted that despite recent advances in breast cancer treatment, the majority of metastatic TNBC patients remain ineligible for immunotherapy and have historically relied on chemotherapy with limited success.
According to Dr. Curigliano, the availability of datopotamab deruxtecan provides physicians with an important new first-line treatment option capable of delivering meaningful clinical benefits for eligible patients while representing substantial progress in managing this aggressive disease.
Safety Profile
The safety evaluation included 319 patients with triple-negative breast cancer who received Datroway at the approved dose of 6 mg/kg during the TROPION-Breast02 study.
The most frequently reported adverse events included:
- Stomatitis
- Nausea
- Alopecia
- Fatigue
- Constipation
- Dry eye
- Keratitis
- Vomiting
- Musculoskeletal pain
- Reduced blood cell counts
- Changes in liver enzyme levels
- Electrolyte abnormalities
Most adverse reactions were manageable with supportive care, dose modifications, or temporary treatment interruption.
Serious adverse events occurred in approximately 17% of patients.
The most common serious complications included:
- Pneumonia
- Vomiting
- COVID-19 infection
- Anemia
One treatment-related fatality associated with interstitial lung disease (ILD)/pneumonitis was reported during the trial.
Healthcare providers are expected to monitor patients closely for pulmonary symptoms, as ILD remains an important safety consideration with several antibody-drug conjugates utilizing the DXd platform.
Daiichi Sankyo Highlights First Survival-Proven TROP2 ADC
Ken Keller, Global Head of Oncology Business and President and CEO of Daiichi Sankyo, described the approval as an important milestone for patients across Europe.
He noted that Datroway is currently the only TROP2-directed antibody-drug conjugate approved in the European Union that has demonstrated an overall survival benefit in the first-line treatment setting for this patient population.
According to Keller, the approval reflects the company’s ongoing commitment to developing innovative oncology therapies capable of addressing significant unmet medical needs while improving long-term outcomes for people living with cancer.
AstraZeneca Emphasizes Clinical Need
Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Hematology Business Unit, highlighted the considerable burden of triple-negative breast cancer throughout Europe.
More than 80,000 people are diagnosed with TNBC across Europe each year, with the disease disproportionately affecting younger women and frequently progressing aggressively once metastatic.
Fredrickson noted that the approval introduces an antibody-drug conjugate with a differentiated clinical profile supported by robust survival data, providing physicians with a valuable new option for patients who previously had few alternatives beyond chemotherapy.
Recognition in International Treatment Guidelines
Even before receiving formal European regulatory approval, the strength of the TROPION-Breast02 data led to Datroway’s inclusion in the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines.
The therapy has been recommended as a Category IA first-line treatment option for metastatic TNBC patients who are not eligible for immunotherapy.
In addition, Datroway has been identified as the preferred first-line treatment for patients whose disease relapses within six months after completing adjuvant therapy.
The treatment also received a score of four out of five on the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS), reflecting the meaningful survival and clinical benefits demonstrated in the pivotal trial.
Expanding Global Availability
The European Union approval follows the U.S. Food and Drug Administration’s approval in May 2026 for the same patient population.
Regulatory reviews are also continuing in several additional regions, including China, Japan, Australia, Canada, Singapore, and Switzerland, with multiple submissions progressing under Project Orbis, an international regulatory collaboration designed to accelerate access to promising cancer therapies.
As additional approvals are granted worldwide, Datroway is expected to become increasingly available to patients with metastatic triple-negative breast cancer who require effective alternatives to traditional chemotherapy. The European Commission’s decision represents another important step in expanding access to a therapy that has demonstrated meaningful improvements in survival, disease control, and tumor response for patients facing one of the most aggressive forms of breast cancer.
About TROPION-Breast02
TROPION-Breast02 is a global, multicenter, randomized, open-label phase 3 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 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 OS and PFS as assessed by BICR. Secondary endpoints include PFS as assessed by 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 365,000 diagnoses globally each year.3,4 In Europe, there are an estimated 81,000 diagnoses of TNBC each year.3,5 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, chemotherapy was the standard 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 a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Datroway (6 mg/kg) is approved in more than 30 countries/regions worldwide 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 more than 45 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, Singapore 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 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.
About the ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of eight ADCs in clinical development crafted from ADC technology discovered in-house by Daiichi Sankyo.
The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs include Enhertu and Datroway, which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939 and DS3790 are being developed by Daiichi Sankyo.
An additional ADC being developed by Daiichi Sankyo is DS3610, which consists of an antibody attached to a novel payload that acts as an agonist of STING.
Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610 and DS3790 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.
About Daiichi Sankyo
Daiichi Sankyo (TSE: 4568) is a global healthcare company committed to becoming a trusted healthcare innovator, transforming the lives of people through its strength in science and technology. The company discovers and develops new standards of care to address diverse medical needs to fulfill its purpose of contributing to the enrichment of quality of life around the world. With a strategic focus on oncology, Daiichi Sankyo is advancing an industry-leading antibody drug conjugate portfolio along with identifying new breakthrough generating technologies to deliver practice-changing medicines to patients, healthcare professionals and society. For more information, please visit www.daiichisankyo.com.