Dato-DXd Approved in China for Previously Treated HR+, HER2– Negative Metastatic Breast Cancer

Datopotamab deruxtecan (Dato-DXd; Datroway) has received approval in China for the treatment of adults with unresectable or metastatic hormone receptor–positive, HER2-negative (immunohistochemistry [IHC] 0, IHC 1+, or IHC 2+/in situ hybridization [ISH] negative) breast cancer who have previously received endocrine therapy and at least 1 line of chemotherapy in the advanced setting.1

The approval follows the FDA’s approval of datopotamab deruxtecan-dlnk (Datroway) for this indication in January 2025 and is supported by the same findings from the phase 3 TROPION-Breast01 trial (NCT05104866), in which Dato-DXd reduced the risk of disease progression or death by 37% compared with investigator’s choice of chemotherapy (HR, 0.63; 95% CI, 0.52-0.76; P < .0001) as assessed by blinded independent central review (BICR).1,2 The median progression-free survival (PFS) was 6.9 months (95% CI, 5.7-7.4) with Dato-DXd vs 4.9 months (95% CI, 4.2-5.5) with chemotherapy.

A confirmed objective response rate (ORR) of 36% (95% CI, 31%-42%) was achieved in the Dato-DXd arm compared with 23% (95% CI, 19%-28%) in the chemotherapy arm, including 2 complete responses (CRs; 0.5%) and 131 partial responses (PRs; 36%) with Dato-DXd vs 0 CRs and 84 PRs (23%) with chemotherapy. The median duration of response (DOR) was 6.7 months (95% CI, 5.6-9.8) with Dato-DXd compared with 5.7 months (95% CI, 4.9-6.8) with chemotherapy.

The final overall survival (OS) results did not reach statistical significance (HR, 1.01; 95% CI, 0.83-1.22). In an exploratory sensitivity analysis adjusting for subsequent antibody-drug conjugate (ADC) treatment, the median OS was 19.1 months with Dato-DXd vs 17.5 months with chemotherapy (HR, 0.86; 95% CI, 0.70-1.06).1

“Despite the progress we have made in managing hormone receptor–positive, HER2-negative metastatic breast cancer, many patients still face limited options once their disease progresses after endocrine therapy and chemotherapy,” Binghe Xu, MD, PhD, director of the Clinical Trial Center of the National Cancer Center at the Cancer Hospital Chinese Academy of Medical Sciences, as well as the China leading principal investigator of TROPIONBreast01, said in a news release. “The approval of [Dato-DXd], a novel TROP2-directed ADC, represents a meaningful step forward in expanding therapeutic choices for patients with breast cancer.”

TROPION-Breast01 Study Breakdown

TROPION-Breast01 is a global, randomized, multicenter, open-label trial evaluating the efficacy and safety of intravenous Dato-DXd administered at 6 mg/kg once every 21 days compared with investigator’s choice of single-agent chemotherapy—eribulin, capecitabine, vinorelbine, or gemcitabine.

Eligible patients included adults with unresectable or metastatic hormone receptor–positive, HER2-negative (IHC 0, IHC 1+, or IHC 2+/ISH–) breast cancer who had progressed on endocrine therapy and were deemed unsuitable for further endocrine treatment per investigator assessment. All patients had received at least 1 prior line of chemotherapy in the advanced setting.

The trial enrolled 732 patients across Africa, Asia, Europe, North America, and South America. Crossover between study arms was not permitted; however, following disease progression or treatment discontinuation, subsequent therapy was allowed at the discretion of the treating physician.

The dual primary end points were PFS per BICR, and OS. Key secondary end points included ORR, DOR, investigator-assessed PFS, disease control rate, time to first subsequent therapy, and safety.

Safety Assessment

In the phase 3 trial, Dato-DXd demonstrated a safety profile consistent with prior reports for ADCs. The most frequently observed adverse effects (AEs; in ≥ 20% of patients), including laboratory abnormalities, were stomatitis, nausea, fatigue, decreased leukocyte counts, decreased calcium levels, alopecia, decreased lymphocyte counts, decreased hemoglobin levels, constipation, decreased neutrophil counts, dry eye, vomiting, increased alanine aminotransferase levels, keratitis, increased aspartate aminotransferase levels, and increased alkaline phosphatase levels.

Grade 3 or higher AEs occurring in more than 0.5% of patients who received Dato-DXd included urinary tract infection (1.9%), COVID-19 infection (1.7%), interstitial lung disease (ILD)/pneumonitis (1.1%), acute kidney injury (0.6%), pulmonary embolism (0.6%), vomiting (0.6%), diarrhea (0.6%), hemiparesis (0.6%), and anemia (0.6%). One grade 5 AE (0.3%) attributed to ILD/pneumonitis was reported.

“Despite considerable advancements in the treatment of hormone receptor–positive breast cancer, new medicines are still needed to tackle the frequent and complex challenge of disease progression following initial therapies,” Dave Fredrickson, executive vice president of the Oncology Hematology Business Unit at AstraZeneca, added in the news release. “We are proud to bring [Dato-DXd] to patients in China for the first time, offering those with metastatic hormone receptor–positive, HER2-negative breast cancer a new and needed option.”

References

1. Datroway approved in China for patients with previously treated metastatic HR positive, HER2 negative breast cancer. News release. Daiichi Sankyo. Accessed August 25, 2025. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202508/20250825_E1.pdf
2. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. FDA. January 17, 2025. Accessed January 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast