Multinational phase 3 trial of datopotamab deruxtecan versus chemotherapy for previously treated inoperable/metastatic HR+/HER2- breast cancer

The multinational phase 3 TROPION-Breast01 study compared the TROP2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator’s choice of chemotherapy (ICC) in inoperable or metastatic HR+/HER2- breast cancer in patients who had received one or two previous lines of breast cancer. Dual primary endpoints were progression-free survival by blinded independent central review and overall survival. The median PFS was significantly longer with Dato-DXd than with ICC (HR 0.63; p<0.001) as was the time to first subsequent therapy (HR 0.53; 95% CI 0.45-0.64). 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 0.62-1.14). The rate of grade ≥ 3 treatment-related adverse events was lower with Dato-DXd than with ICC (20.8% versus 44.7%). The authors conclude that these results support Dato-DXd as a novel treatment option for patients with inoperable/metastatic HR+/HER2- breast cancer who have received one or two previous lines of chemotherapy in this setting.