Multinational phase 3 trial of datopotamab deruxtecan for untreated, advanced triple-negative breast cancer

Patients with previously untreated, advanced triple-negative breast cancer (TNBC) who are not candidates for immunotherapy have limited treatment options and a poor prognosis. In the multinational phase 3 TROPION-Breast02 trial, patient with previously untreated, locally recurrent inoperable or metastatic TNBC were randomized 1:1 to datopotamab deruxtecan (Dato-DXd; 6 mg/kg intravenously every 3 weeks; n=323) or investigator’s choice of chemotherapy (n=322). Co-primary endpoints were progression-free survival (PFS; blinded independent central review) and overall survival (OS). Median PFS was 10.8 months with Dato-DXd and 5.6 months with chemotherapy (HR 0.57; p<0.0001); median OS was 23.7 months and 18.7 months (HR 0.79; p=0.029); treatment-related adverse events of grade ≥ 3 were reported in 33% and 29%, and TRAEs leading to treatment discontinuation in 4% and 7%. There were no treatment-related deaths in either arm. The authors conclude that Dato-DXd demonstrated significantly improved PFS and OS versus chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option.