112 First-Line (1L) Datopotamab Deruxtecan (Dato-DXd) vs Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer (mTNBC) for Whom Immunotherapy Was Not an Option: Primary Results From the Randomized, Phase 3 TROPION-Breast02 Trial

Background

Treatment options are limited and prognosis is poor for the approximately 70% of patients with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy is not an option; moreover, approximately half of patients with mTNBC do not receive treatment beyond first-line. Here, we report the primary analysis from the TROPION-Breast02 study (NCT05374512).

Methods

Adult patients with previously untreated locally recurrent inoperable or mTNBC, for whom immunotherapy was not an option, were randomly assigned 1:1 to datopotamab deruxtecan (Dato-DXd) (6 mg/kg intravenous every 3 weeks) or investigator’s choice of chemotherapy (ICC; [nab]-paclitaxel/ capecitabine/eribulin mesylate/carboplatin). Randomization was stratified by geographic location, PD-L1 status and disease-free interval history (de novo vs disease-free interval [DFI] 0–12 months vs DFI >12 months; DFI defined as time from completion of treatment with curative intent to first documented local/distant disease recurrence). Dual primary end points were overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1.

Results

A total of 644 patients were randomized (Dato-DXd: 323; ICC: 321). At data cutoff (August 25, 2025), median study follow-up was 27.5 months. Results are shown in the Table. There was a statistically significant, 5 months or more improvement in both median OS and PFS by BICR with Dato-DXd compared with ICC OS (HR, 0.79; 95% CI, 0.64-0.98; P = .0291), and PFS (HR, 0.57; 95% CI, 0.47-0.69; P <.0001). Despite more than double the duration of treatment in the Dato-DXd arm, rates of grade 3 or higher TRAEs were similar and discontinuations were lower vs ICC.

Conclusions

TROPION-Breast02 met both dual primary end points; first-line Dato-DXd demonstrated statistically significant and clinically meaningful OS and PFS improvement over chemotherapy in patients with locally recurrent inoperable or mTNBC for whom immunotherapy was not an option. The Dato-DXd safety profile was manageable. Results support Dato-DXd as the new first-line standard of care.

Previously presented at ESMO 2025, Final Publication Number: LBA21, Rebecca A Dent et al. Reused with permission.

This trial is sponsored by AstraZeneca. In July 2020, Daiichi-Sankyo entered into a global development and commercialization collaboration with AstraZeneca for datopotamab deruxtecan (Dato-DXd).

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Helen Kitchen of Ashfield MedComms (Macclesfield, UK), an Inizio company, in accordance with Good Publication Practice (GPP) guidelines (http://www.ismpp.org/gpp-2022), and was funded by AstraZeneca.