Japan Approves Datroway for HR+ HER2- Breast Cancer

The approval of Datroway by the Japan Ministry of Health, Labour and Welfare (MHLW) is based on results from the TROPION-Breast01 phase III trial. In this trial, 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  compared to 4.9 months in those treated with chemotherapy.

TROPION-Breast01 is a global, randomized, multicenter, open-label phase III trial evaluating the efficacy and safety of intravenous Datroway (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 progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease.

In TROPION-Breast01, adverse reactions occurred in 93.6% (337/360 patients) of the 360 patients (including 31 Japanese patients) in the Datroway  (6 mg/kg) arm. The most common adverse reactions included nausea (51.1%), stomatitis (50.0%), alopecia (36.4%), fatigue (23.6%), and dry eye (21.7%). In Japanese patients, interstitial lung disease (ILD) occurred in 6.5% of patients treated with Datroway .  The dual primary endpoints of TROPION-Breast01 are PFS as assessed by BICR and overall survival. 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. 

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 Sep 12:JCO2400920. doi: 10.1200/JCO.24.00920. Online ahead of print. 

"This first global approval of Datroway provides patients in Japan with metastatic HR positive, HER2 negative breast cancer a new alternative to conventional chemotherapy, which is often associated with poor response rates,” said Wataru Takasaki, Senior Advisor, Daiichi Sankyo. “Datroway also is the second DXd antibody drug conjugate approved in Japan based on technology invented by Daiichi Sankyo, emphasizing our commitment to creating new, innovative standards of care for patients with cancer.”