Datroway (datopotamab deruxtecan) approved in the EU for patients with previously treated metastatic HR Positive, HER2 negative breast cancer- Daiichi Sankyo + AstraZeneca

Datroway (datopotamab deruxtecan) has been approved in the European Union (EU) for the treatment of adult patients with unresectable or metastatic hormone receptor  (HR) positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received endocrine therapy and at least one line of chemotherapy in the advanced setting.  The approval by the European Commission follows the positive opinion of the Committee for Medical Products for Human Use (CHMP)  of the EMA and is based on results from the TROPION-Breast01 phase III trial.

In TROPION-Breast01, Datroway  significantly reduced the risk of disease progression or death by 37% compared to investigator’s choice of chemotherapy (hazard ratio [HR]=0.63; 95% confidence interval [CI]: 0.52-0.76; p<0.0001) in patients with HR positive, HER2 negative metastatic breast cancer as assessed by blinded independent central review (BICR). Median progression free survival (PFS) was 6.9 months in patients treated with Datroway versus 4.9 months with chemotherapy. A confirmed objective response rate (ORR) of 36% was observed in the Datroway arm compared to an ORR of 23% observed in the chemotherapy arm. The median duration of response (DoR) was 6.7 months (95% CI: 5.6-9.8) in the Datroway arm compared to 5.7 months (95% CI: 4.9-6.8) in the chemotherapy arm. The final overall survival (OS) results of the trial 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]) and may have been affected by subsequent ADC treatment.

Grade 3 or higher adverse events from a pooled safety analysis of two clinical studies, including 443 patients who received Datroway (6 mg/kg) for a median duration of 6.2 months (range  0.7-28.5), were 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%) and pneumonia (1.1%). Grade 5 adverse events occurred in 0.7% of patients due to interstitial lung disease/pneumonitis, dyspnea and sepsis.

TROPION-Breast01 is a global, randomized, multicenter, open-label phase III trial evaluating the efficacy and safety of intravenous datopotamab deruxtecan (6 mg/kg) once per 21-day cycle versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one prior line of chemotherapy for unresectable or metastatic disease. Following disease progression or discontinuation of datopotamab deruxtecan or chemotherapy, patients had the option to receive a subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted. TROPION-Breast01 enrolled 732 patients in Africa, Asia, Europe, North America and South America. 

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by BICR and overall survival (OS). Key secondary endpoints include overall response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. The PFS data and additional results for key secondary endpoints of TROPION-Breast01 were published in the Journal of Clinical Oncology. The OS data were presented at a Virtual Plenary session hosted by the European Society for Medical Oncology (ESMO) in February 2025.

“Treating metastatic HR positive, HER2 negative breast cancer presents challenges, particularly treatment resistance and disease progression that occur following endocrine-based therapy and initial chemotherapy,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “DATROWAY represents the second antibody drug conjugate approved for breast cancer 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.”

“Though the HR positive breast cancer 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 approval of DATROWAY, patients in the EU with HR positive, HER2 negative breast cancer now have a new and needed alternative to conventional chemotherapy.”

"With the majority of breast cancer 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 Dr. Barbara Pistilli, 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.”

See citation- Bardia A, Jhaveri K, Im SA, Pernas S et al. Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor–Positive Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer: Primary Results From TROPION-Breast01.  J Clin Oncol   2024 43, 285 DOI:10.1200/JCO.24.00920