DATROWAY® (Datopotamab Deruxtecan) Receives EU Approval for Previously Treated Metastatic HR+/HER2- Breast Cancer
Key Insights
DATROWAY, a TROP2 (search)-directed antibody drug conjugate (ADC), has been approved in the European Union for treating adult patients with unresectable or metastatic HR+/HER2- breast cancer (search) who have received endocrine therapy and at least one line of chemotherapy.
The approval is based on the TROPION-Breast01 phase 3 trial, which showed DATROWAY reduced the risk of disease progression or death by 37% compared to chemotherapy, with a median PFS of 6.9 months versus 4.9 months.
This marks the second ADC approved for breast cancer (search) based on Daiichi Sankyo's DXd technology and the third medicine from their oncology pipeline to receive EU approval, highlighting their commitment to developing innovative cancer treatments.
The European Commission has approved DATROWAY® (datopotamab deruxtecan) for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 negative breast cancer (search) who have received endocrine therapy and at least one line of chemotherapy in the advanced setting.
DATROWAY is a specifically engineered TROP2 (search)-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized with AstraZeneca. The approval follows the positive opinion of the Committee for Medical Products for Human Use of the European Medicines Agency and is based on results from the TROPION-Breast01 phase 3 trial.
TROPION-Breast01 Trial Results
In the pivotal TROPION-Breast01 trial, DATROWAY demonstrated significant clinical benefit compared to investigator's choice of chemotherapy:
- 37% reduction in the risk of disease progression or death (hazard ratio [HR]=0.63; 95% confidence interval [CI]: 0.52-0.76; p<0.0001)
- Median progression-free survival (PFS) of 6.9 months versus 4.9 months with chemotherapy
- Confirmed objective response rate (ORR) of 36% compared to 23% with chemotherapy
- Median duration of response (DoR) of 6.7 months (95% CI: 5.6-9.8) versus 5.7 months (95% CI: 4.9-6.8) with chemotherapy
The final overall survival (OS) results did not achieve statistical significance (median OS of 18.6 months in the DATROWAY arm versus 18.3 months in the chemotherapy arm [HR 1.01; 95% CI: 0.83-1.22]). Researchers note these results may have been affected by subsequent ADC treatment.
"With the majority of breast cancer (search) cases historically considered HR positive, HER2 negative, additional treatment options are needed to improve outcomes for patients with metastatic disease that continues to progress following endocrine-based therapy and initial chemotherapy," said Barbara Pistilli, MD, Head of the Breast Cancer Unit in the Medical Oncology Department of Gustave Roussy Cancer Center, Villejuif, France. "The approval of DATROWAY in the EU will provide these patients with a new treatment option that can help slow the progression of this disease."
Safety Profile
The safety profile of DATROWAY was assessed in a pooled analysis of two clinical studies, including 443 patients who received DATROWAY (6 mg/kg) for a median duration of 6.2 months. Grade 3 or higher adverse events included:
- Stomatitis (7.9%)
- Fatigue (4.3%)
- Anemia (3.2%)
- AST increased (2.7%)
- Vomiting (1.6%)
- ALT increased (1.6%)
- Nausea (1.4%)
- Urinary tract infection (1.4%)
- COVID-19 (1.1%)
- Decreased appetite (1.1%)
- Neutropenia (1.1%)
- Pneumonia (1.1%)
Grade 5 adverse events occurred in 0.7% of patients due to interstitial lung disease (search)/pneumonitis (search), dyspnea, and sepsis.
Addressing an Unmet Need in HR+/HER2- Breast Cancer
Breast cancer (search) remains the second most common cancer and one of the leading causes of cancer-related deaths worldwide, with more than two million cases diagnosed in 2022 and over 665,000 deaths globally. In Europe alone, approximately 557,000 cases of breast cancer are diagnosed annually.
Approximately 70% of diagnosed cases are considered HR positive, HER2 negative breast cancer (search). While endocrine therapy is widely used in early lines of treatment for metastatic HR positive breast cancer (search), its efficacy is often limited after initial treatment.
"Though the HR positive breast cancer (search) treatment landscape has evolved in the last several years, disease progression on front-line therapies remains a common and complex challenge for patients with metastatic disease," said Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca. "With today's approval of DATROWAY, patients in the EU with HR positive, HER2 negative breast cancer (search) now have a new and needed alternative to conventional chemotherapy."
Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc., added, "DATROWAY represents the second antibody drug conjugate approved for breast cancer (search) based on Daiichi Sankyo's DXd technology and the third medicine to be approved in the EU from our oncology pipeline, underscoring our commitment to creating new medicines for patients with cancer."
About DATROWAY
DATROWAY (datopotamab deruxtecan) is a TROP2 (search)-directed ADC designed using Daiichi Sankyo's proprietary DXd ADC Technology. It is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to topoisomerase I inhibitor payloads via tetrapeptide-based cleavable linkers.
The drug is now approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative breast cancer (search) who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
A comprehensive global clinical development program is underway with more than 20 trials evaluating DATROWAY across multiple cancers, including non-small cell lung cancer, triple negative breast cancer (search), and HR positive, HER2 negative breast cancer (search). The program includes eight phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating DATROWAY as a monotherapy and in combination with other anticancer treatments.
Expanding ADC Portfolio
DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo and one of the most advanced programs in AstraZeneca's ADC scientific platform. The approval represents another milestone in the global collaboration between Daiichi Sankyo and AstraZeneca, which began with ENHERTU® in March 2019 and expanded to include DATROWAY in July 2020.
The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house. The company continues to advance its research in this promising area of cancer treatment, with several other ADCs in various stages of development.