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 randomised, phase 3 TROPION-Breast02 trial

The phase 3 TROPION-Breast02 trial evaluated Dato-DXd, a TROP2-directed antibody drug conjugate, compared with investigator’s choice chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) who were not eligible for immunotherapy. Eligible patients included those with PD-L1 low tumors or PD-L1 high disease that relapsed after prior PD-(L)1 therapy, those with comorbidities preventing immunotherapy, or those without access to PD-(L)1 inhibitors.

Dato-DXd produced a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) compared with chemotherapy. Median PFS was 10.8 months with Dato-DXd versus 5.6 months with chemotherapy, representing a 43 percent reduction in the risk of progression or death. Median OS was also prolonged, with a 21 percent reduction in the risk of death. Twelve-month OS rates were 75 percent for Dato-DXd and 68 percent for chemotherapy, while 18-month rates were 61 percent and 51 percent. Efficacy benefits were consistent across subgroups, including patients with stable brain metastases.

The confirmed overall response rate was more than double with Dato-DXd, and complete responses were more than three times higher. The median duration of response exceeded one year. Despite more than twice the treatment duration, grade 3 or higher and serious treatment-related adverse events were similar between groups, and fewer patients discontinued Dato-DXd. Common adverse events included nausea, stomatitis, and alopecia. Ocular surface and interstitial lung disease events were typically low grade and manageable with routine monitoring.

These data support Dato-DXd as a new first-line standard for patients with previously untreated mTNBC who are not candidates for immunotherapy.