Multinational phase 3 trial of datopotamab deruxtecan versus chemotherapy for HR-positive HER2-negative mBC: final OS analysis of TROPION-Breast01

The multinational phase 3 TROPION-Breast01 study demonstrated clinically meaningful improvement in progression-free survival by blinded independent central review with the TROP2-directed antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) versus investigator’s choice of chemotherapy (ICC) in patients with previously treated inoperable or metastatic HR-positive HER2-negative (HR+ HER2-) breast cancer. Final overal survival results have now been published. Median duration of follow-up was 22.8 months. There was no significant OS benefit with Dato-DXd versus ICC (HR 1.01; p=0.9445). Use of ADCs (trastuzumab deruxtecan and sacituzumab govitecan) as subsequent therapy was imbalanced: 12.3% in the Dato-DXd group and 24.0% in the ICC group. Secondary efficacy endpoints (PFS by investigator, objective response rate, duration of response, disease control rate at 12 weeks, time to subsequent therapy or death) continued to favor Dato-DXd at this final analysis. The overall safety profile of Dato-DXd remained favorable compared with ICC. The authors conclude that TROPION-Breast01 did not meet its OS endpoint, likely due to imbalance between the two groups in subsequent ADC use.