Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01

Abstract

Purpose: The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer.

Methods: Adult patients with inoperable/metastatic HR+/HER2‒ breast cancer, who had disease progression on endocrine therapy, for whom endocrine therapy was unsuitable, and had received one to two previous lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1:1 to Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS).

Results: Patients were randomly assigned to Dato-DXd (n = 365) or ICC (n = 367). Dato-DXd significantly reduced the risk of progression or death versus ICC (PFS by BICR hazard ratio [HR], 0.63 [95% CI, 0.52 to 0.76]; P < .0001). Consistent PFS benefit was observed across subgroups. Although OS data were not mature, a trend favoring Dato-DXd was observed (HR, 0.84 [95% CI, 0.62 to 1.14]). The rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was lower than ICC (20.8% v 44.7%). The most common TRAEs (any grade; grade ≥3) were nausea (51.1%; 1.4%) and stomatitis (50%; 6.4%) with Dato-DXd and neutropenia (grouped term, 42.5%; 30.8%) with ICC.

Conclusion: Patients receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS and a favorable and manageable safety profile, compared with ICC. Results support Dato-DXd as a novel treatment option for patients with inoperable/metastatic HR+/HER2‒ breast cancer who have received one to two previous lines of chemotherapy in this setting.

Trial registration: ClinicalTrials.gov NCT05104866.

FIG 1.

CONSORT diagram. Dato-DXd, datopotamab deruxtecan; DCO, data cutoff; ICC, investigator's choice of chemotherapy.

FIG 2.

(A) PFS by blinded independent central review and (B) TFST (intention-to-treat population). Dato-DXd, datopotamab deruxtecan; HR, hazard ratio; ICC, investigator's choice of chemotherapy; PFS, progression-free survival; TFST, time to first subsequent therapy.

FIG 3.

Subgroup analysis of PFS by blinded independent central review (intention-to-treat population). Size of circle is proportional to the number of events across both treatment groups. ^aAsian = Patients from China, Japan, South Korea, Taiwan. CDK4/6, cyclin-dependent kinase 4/6; Dato-DXd, datopotamab deruxtecan; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; ICC, investigator's choice of chemotherapy; PFS, progression-free survival.

FIG A1.

PFS by investigator assessment (intention-to-treat population). Dato-DXd, datopotamab deruxtecan; HR, hazard ratio; ICC, investigator's choice of chemotherapy; PFS, progression-free survival.