Datopotamab deruxtecan showed no overall survival benefit versus investigator's choice chemotherapy in metastatic HR-positive breast cancer.

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Annals of oncology : official journal of the European Society for Medical Oncology Published June 4, 2026 Medically reviewed June 4, 2026 Study authors: Pistilli B, Jhaveri K, Im S-A, Pernas S, De Laurentiis M, Wang S, Martínez Jañez N, Borges G, Cescon… PubMed ↗ NCT05104866 ↗ DOI ↗ By Dr. Sofia Müller, MD · Lifespan & Whole-Person Care

Key Takeaway

Consider datopotamab deruxtecan for previously treated metastatic HR-positive/HER2-negative breast cancer despite neutral OS.

This Phase III randomized controlled trial evaluated datopotamab deruxtecan versus investigator's choice chemotherapy in patients with inoperable or metastatic HR-positive/HER2-negative breast cancer. The population included those who had disease progression on endocrine therapy and for whom endocrine therapy was unsuitable, and who had received one to two prior lines of chemotherapy in the inoperable or metastatic setting. The sample size was not reported and the setting was not reported.

The intervention was datopotamab deruxtecan at 6 mg/kg every 3 weeks, compared with investigator's choice of chemotherapy including eribulin, capecitabine, vinorelbine, or gemcitabine. Overall survival by blinded independent central review did not reach statistical significance, with a hazard ratio of 1.01 and a 95% confidence interval of 0.83-1.22. The P value was 0.9445. Use of ADCs as subsequent therapy was imbalanced, with 12.3% in the Dato-DXd arm versus 24.0% in the investigator's choice chemotherapy arm.

The overall safety profile of Dato-DXd remained favorable compared with investigator's choice chemotherapy, and no new safety signals were observed with longer follow-up. The overall safety profile of Dato-DXd remained favorable compared with investigator's choice chemotherapy. Follow-up duration was 0.7 months.

Key limitations include the imbalance in the use of ADCs as subsequent therapy, which may affect OS results. The totality of efficacy and safety data supports Dato-DXd as a new treatment option for patients with previously treated, inoperable or metastatic HR-positive/HER2-negative breast cancer.

Study Details

Study typeRct

EvidenceLevel 2

Follow-up0.7 mo

PublishedMay 2026

PMID41448362

TrialNCT05104866

View Original Abstract ↓

BACKGROUND: The TROPION-Breast01 study (NCT05104866) demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) by blinded independent central review (BICR) with the trophoblast cell-surface antigen 2-directed antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in patients with previously treated, inoperable/metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report results from the final overall survival (OS) analysis. PATIENTS AND METHODS: Patients with inoperable/metastatic HR-positive/HER2-negative breast cancer, who had disease progression on endocrine therapy and for whom endocrine therapy was unsuitable, and had received one to two prior lines of chemotherapy in the inoperable/metastatic setting were randomly assigned in a 1 : 1 ratio to Dato-DXd (6 mg/kg every 3 weeks) or ICC (eribulin/capecitabine/vinorelbine/gemcitabine). Dual primary endpoints were PFS by BICR and OS. RESULTS: At data cut-off, median follow-up was 22.8 months. OS for the Dato-DXd versus ICC arm did not reach statistical significance (hazard ratio 1.01, 95% confidence interval 0.83-1.22, P = 0.9445). Use of ADCs (trastuzumab deruxtecan and sacituzumab govitecan) as subsequent therapy was imbalanced: 12.3% in the Dato-DXd arm versus 24.0% in the ICC arm. Secondary efficacy endpoints (PFS by investigator assessment, objective response rate, duration of response, disease control rate at 12 weeks, time to first and second subsequent therapy or death, and time to second progression or death) continued to favor Dato-DXd at this final analysis. The overall safety profile of Dato-DXd remained favorable compared with ICC, and no new safety signals were observed with longer follow-up. CONCLUSIONS: TROPION-Breast01 met its dual primary endpoint of PFS by BICR. While there was no statistically significant improvement in the dual primary endpoint of OS with Dato-DXd versus ICC, subsequent ADC treatment may have affected OS results. The totality of efficacy and safety data supports Dato-DXd as a new treatment option for patients with previously treated, inoperable/metastatic HR-positive/HER2-negative breast cancer.