European Commission Approves First-Line Dato-DXd for Immunotherapy-Ineligible Metastatic TNBC

The European Commission has approved datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) as monotherapy for the first-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.¹

The decision follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

The approval was supported by findings from the phase 3 TROPION-Breast02 trial (NCT05374512), which were presented at the 2025 ESMO Congress.² In the trial, Dato-DXd (n = 323) produced a median overall survival (OS) of 23.7 months (95% CI, 19.8-25.6) vs 18.7 months (95% CI, 16.0-21.8) with investigator’s choice of chemotherapy (n = 321), a 5.0-month improvement (HR, 0.79; 95% CI, 0.64-0.98; P = .0291).^1,2 The agent also reduced the risk of disease progression or death by 43% vs chemotherapy by blinded independent central review (BICR; HR, 0.57; 95% CI, 0.47-0.69; P < .0001).

“Despite recent advances, more than two-thirds of patients are not candidates for immunotherapy and have had limited options beyond chemotherapy,” Giuseppe Curigliano, MD, PhD, stated in a news release. “This approval of Dato-DXd provides a new treatment option for eligible patients and represents meaningful progress.”

Curigliano is the director of the Early Drug Development Division at the European Institute of Oncology and a professor of medical oncology in the Department of Oncology and Haemato-Oncology at the University of Milan in Italy. He also served as an investigator on TROPION-Breast02.

How was the TROPION-Breast02 trial designed?

TROPION-Breast02 was a global, multicenter, randomized, open-label trial that evaluated Dato-DXd vs investigator’s choice of chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. The population included patients whose tumors did not express PD-L1, as well as those with PD-L1–expressing tumors who were not eligible to receive immunotherapy because of prior exposure in early-stage disease, comorbidities, or a lack of access in their geography. Enrollment permitted patients with de novo or recurrent disease regardless of disease-free interval, as well as those with poor prognostic features, including stable brain metastases.

A total of 644 patients were enrolled at sites in Africa, Asia, Europe, North America, and South America and were randomly assigned 1:1 to receive Dato-DXd at 6 mg/kg intravenously every 3 weeks or chemotherapy comprising paclitaxel, nab-paclitaxel (Abraxane), capecitabine, carboplatin, or eribulin.^1,2 OS and PFS by BICR served as the dual primary end points. Secondary end points included investigator-assessed PFS, objective response rate (ORR), duration of response, and safety.

What additional efficacy and safety findings supported the EU approval of first-line Dato-DXd for TNBC?

The median PFS by BICR was 10.8 months (95% CI, 8.6-13.0) with Dato-DXd vs 5.6 months (95% CI, 5.0-7.0) with chemotherapy.² Treatment with the ADC was associated with an ORR of 62.5% vs 29.3% with chemotherapy.¹ The safety profile of Dato-DXd in TROPION-Breast02 was deemed consistent with that observed in previous breast cancer trials of the agent.

On the basis of the TROPION-Breast02 results, Dato-DXd has been incorporated into the ESMO Clinical Practice Guidelines as a category IA first-line option for the treatment of patients with metastatic TNBC who are not candidates for immunotherapy, and it is the preferred option for patients who relapse within 6 months of completing adjuvant therapy. The agent also received a score of 4 out of 5 on the ESMO Magnitude of Clinical Benefit Scale.

What is the broader regulatory status of Dato-DXd for TNBC and other cancers?

Dato-DXd was approved in the United States in May 2026 for the same first-line, immunotherapy-ineligible metastatic TNBC indication.³ It is also approved in more than 45 countries for the treatment of patients with pretreated hormone receptor–positive, HER2-negative (immunohistochemistry [IHC] 0, IHC 1+, or IHC 2+/in situ hybridization negative) breast cancer based on the TROPION-Breast01 trial and is available in the US under accelerated approval for pretreated, EGFR-mutated non–small cell lung cancer based on findings from the TROPION-Lung05 and TROPION-Lung01 trials.¹ Additional regulatory reviews for Dato-DXd in the first-line TNBC setting are underway in China and Japan, as well as in Australia, Canada, Singapore, and Switzerland as part of Project Orbis.

References

1. Datroway approved in the EU as only TROP2-directed medicine with overall survival benefit for the 1st-line treatment of patients with metastatic TNBC who are not candidates for immunotherapy. News release. AstraZeneca. July 31, 2026. Accessed July 31, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/datroway-approved-in-eu-for-tnbc.html
2. Dent R, Shao Z, Schmid P, et al. Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial. Ann Oncol. 2026;S0923-7534(26)00130-4. doi:10.1016/j.annonc.2026.03.008
3. Datroway approved in the U.S. as first TROP2 directed antibody drug conjugate for first-line treatment of patients with metastatic triple negative breast cancer who are not PD-1/PD-L1 inhibitor candidates. News release. Daiichi Sankyo. May 22, 2026. Accessed July 31, 2026. https://daiichisankyo.us/web/dsi/press-releases/-/article/datroway-approved-in-the-us-as-first-trop2-directed-antibody-drug-conjugate-for-first-line-treatment-of-patients-with-metastatic-triple-negative-breast-cancer-who-are-not-pd-1pd-l1-inhibitor-candidates