FDA Approves Dato-DXd for Metastatic Triple-Negative Breast Cancer

The FDA has approved datopotamab deruxtecan-dlnk (dato-DXd; Datroway) for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.¹

This approval positions dato-DXd as a potential new standard of care in the first-line setting, offering a potent TROP2-directed option for the approximately 70% of patients with mTNBC who are ineligible for immunotherapy due to low PD-L1 expression or other clinical contraindications.²

Pivotal Trial Data: TROPION-Breast02

The regulatory decision was supported by primary results from the global, randomized, open-label phase 3 TROPION-Breast02 trial (NCT05374512).³ The study compared dato-DXd monotherapy (6.0 mg/kg every 3 weeks) against investigator’s choice of chemotherapy, which included eribulin, capecitabine, vinorelbine, or gemcitabine.

The trial met its dual primary end points of progression-free survival (PFS) and OS, demonstrating a transformative benefit over traditional cytotoxic agents.⁴

The 43% reduction in the risk of disease progression or death underscores the efficacy of this antibody-drug conjugate (ADC). Notably, the median OS improvement of 5.0 months represents a clinically meaningful extension of life in a disease state historically characterized by rapid progression and poor prognosis.

“[Dato-DXd] is the first and only medicine to significantly prolong [OS] in the first-line setting compared to chemotherapy in patients with metastatic [TNBC] who are not candidates for immunotherapy,” trial investigator Tiffany A. Traina, MD, FASCO, section head of the Triple Negative Breast Cancer Clinical Research Program at Memorial Sloan Kettering Cancer Center, stated in a press release on the approval.⁵ “This approval will bring a much-needed treatment option for these patients.”

TROPION-Breast02 Design

In the open-label, international TROPION-Breast02 trial, 644 patients with previously untreated locally recurrent inoperable or metastatic TNBC not eligible for immunotherapy were assigned to receive dato-DXd or investigator’s choice of chemotherapy. Patients whose tumors did not express PD-L1 as well as those with PD-L1–positive tumors who could not receive immunotherapy due to prior exposure in earlier disease settings, comorbidities, or immunotherapy not being available in their region were eligible for enrollment on the trial. The study also included patients with de novo or recurrent disease regardless of disease-free interval and those with poor prognostic factors like brain metastases.

The trial’s dual primary end points were PFS per blinded independent central review and OS. Key secondary end points included investigator-evaluated PFS, ORR, DOR, disease control rate, and safety.

Safety and Tolerability

The safety profile of Dato-DXd in the TROPION-Breast02 trial was consistent with previous reports, emphasizing a manageable but distinct toxicity profile compared with other ADCs in the class.

• Gastrointestinal and Oral: Stomatitis and oral mucositis were the most frequent treatment-related adverse events (TRAEs). Any-grade stomatitis occurred in 57% of patients who received dato-DXd, and grade 3 or higher events occurred in 8%.
• Ocular: Dry eye (24%) and keratitis, which was an AE of special interest, were observed.
• Hematologic: Grade 3 or higher neutropenia (3%) and anemia (2%) were also noted.

Dosing and Administration

Dato-DXd is currently administered in 6.0 mg/kg intravenously once every 3 weeks. Clinicians should be prepared to manage oral toxicities through the use of steroid mouthwashes and dose titrations where necessary, as noted in other TROPION trials.²

References

1. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic triple-negative breast cancer. News release. FDA. May 22, 2026. Accessed May 22, 2026. https://tinyurl.com/2s45pcrr
2. DATROWAY® (datopotamab deruxtecan-dlnk) granted Priority Review in the US as 1st-line treatment for patients with metastatic triple-negative breast cancer who are not candidates for immunotherapy. News release. AstraZeneca. February 3, 2026. Accessed May 22, 2026. https://tinyurl.com/4nex58hb
3. Dent RA, Shao Z, Schmid P, et al. First-line datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option: Primary results from the randomised, phase 3 TROPION-Breast02 trial. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA21.
4. Datroway demonstrated statistically significant and clinically meaningful improvement in overall survival as 1st-line therapy for patients with metastatic triple-negative breast cancer for whom immunotherapy was not an option in TROPION-Breast02. News release. AstraZeneca. October 6, 2025. Accessed May 22, 2026. https://tinyurl.com/34wfs9xj
5. 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 May 22, 2026. https://tinyurl.com/mfpsw7ne