Dato-DXd Improves Survival in Recurrent Inoperable/Metastatic TNBC

Dato-DXd's investigators will present the full data at an upcoming medical meeting and share them with regulatory authorities.

Datopotamab deruxtecan-dlnk (dato-DXd; Datroway) met both primary end points of overall survival (OS) and progression-free survival (PFS) among patients treated in the first-line setting for recurrent inoperable or metastatic triple-negative breast cancer (TNBC) ineligible for immunotherapy in the phase 3 TROPION-Breast02 trial (NCT05374512), according to a news release from the drug’s developer, AstraZeneca.1

According to the news release, for the approximately 70% of patients for whom immunotherapy is not an option in TNBC, the first-line option is chemotherapy. In the TROPION-Breast02 study, dato-DXd exhibited a statistically significant improvement in both OS and PFS outcomes compared to investigator’s choice of chemotherapy for this patient population.

Additionally, the safety profile of dato-DXd was consistent with previous clinical trials evaluating the agent in breast cancer. The investigators will present the full data at an upcoming medical meeting and share them with regulatory authorities.

“TROPION-Breast02 is the only trial ever to show an [OS] benefit in the first-line treatment of patients with metastatic [TNBC] for whom immunotherapy is not an option,” Susan Galbraith, executive vice president of Oncology Hematology Research and Development at AstraZeneca, said in the news release.1 “We expect today’s results will mark an inflection point in the treatment of these patients who have the poorest prognosis of any type of breast cancer and urgently need better options.”

Patients in the phase 3 trial were randomly assigned 1:1 to receive dato-DXd or investigator’s choice of chemotherapy, which included paclitaxel, nab-paclitaxel, capecitabine, carboplatin, or eribulin. Those who were eligible included adults whose tumors did not express PD-L1 and those who could not receive immunotherapy due to exposure for an earlier stage of disease, comorbidities, or inaccessibility. Additionally, patients with de novo disease and those with poor prognostic factors, including brain metastases, were eligible for enrollment.

Those treated in the investigational arm received dato-DXd at 100 mg via intravenous infusion.2 Patients in the chemotherapy arm received treatment intravenously, with paclitaxel or nab-paclitaxel given in the absence of prior receipt of taxanes overall or in the adjuvant or neoadjuvant setting and a disease-free interval (DFI) of greater than 12 months. Capecitabine, carboplatin, or eribulin was provided if prior taxanes were given and the DFI was 12 months or fewer.

The coprimary end points of the trial included PFS assessed by blinded independent central review and OS. Key secondary end points included PFS per investigator assessment, objective response rate, duration of response, disease control rate, pharmacokinetics, and safety.

The developers engineered dato-DXd as a TROP2-directed antibody drug conjugate (ADC) using a proprietary DXd ADC technology. It contains a humanized anti-TROP2 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads via tetrapeptide-based cleavable linkers.

Those with histologically or cytologically confirmed disease who received no prior chemotherapy or systemic anticancer therapy for metastatic or locally recurrent inoperable breast cancer were eligible for trial enrollment. Additional eligibility criteria included at least 1 measurable lesion not previously irradiated, an ECOG performance status of 0 or 1, and adequate organ and bone marrow function within 7 days of assignment.

Patients ineligible for treatment included those with evidence of uncontrolled systemic diseases, hypertension, or history of allogenic organ transplant; those with a history of primary malignancy except for ones treated with curative intent with no known activity for at least 3 years prior to first study dose; and those with uncontrolled infections requiring intravenous antibiotics, antivirals, or antifungals.

References

1. 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 October 6, 2025. https://tinyurl.com/5a8a4r69
2. A study of dato-DXd versus investigator's choice chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer, who are not candidates for PD-1/​PD-L1 inhibitor therapy (TROPION-Breast02). ClinicalTrials.gov. Updated July 10, 2025. Accessed October 6, 2024. https://tinyurl.com/5ed44nsm