Datopotamab Deruxtecan Significantly Improves Progression-Free Survival for Patients With HR-Positive, HER2-Negative Breast Cancer

Primary Results From TROPION-Breast01 

Primary results from the TROPION-Breast01 trial demonstrated that datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody drug conjugate, significantly improved progression-free survival (PFS) compared to investigator’s choice of chemotherapy for patients with inoperable or metastatic hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer. 

According to Aditya Bardia, MD, Jonsson Comprehensive Cancer Center, Los Angeles, California, and coauthors, “Until recently, for patients with endocrine-resistant disease or patients ineligible for endocrine therapy, single-agent chemotherapy was the standard of care…however, chemotherapy is associated with limited clinical benefit and substantial toxicities that negatively affect the quality of life of patients.”

In this open-label study, 711 patients who received 1 to 2 prior lines of chemotherapy were randomized on a 1-to-1 basis to receive either 6 mg/kg of datopotamab deruxtecan once every 3 weeks (n = 360), or investigator’s choice of single-agent eribulin, capecitabine, vinorelbine, or gemcitabine (n = 351) until unacceptable toxicity or investigator-assessed radiologic disease progression. Primary end points included PFS by blinded independent central review and overall survival (OS). Key secondary end points included safety and tolerability. 

At a median follow-up of 10.8 months, datopotamab deruxtecan reduced the risk of progression or death by 37% compared to single-agent chemotherapy (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.52 to 0.76; P < .0001). The median PFS was 6.9 months in the datopotamab deruxtecan arm and 4.9 months in the single-agent chemotherapy arm. Though OS data was immature at the time of analysis, trends favored datopotamab deruxtecan (HR, 0.84; 95% CI, 0.62 to 1.14). 

Grade ≥3 treatment-related adverse events occurred in 20.8% of patients in the datopotamab deruxtecan arm and 44.7% of patients in the single-agent chemotherapy arm and serious treatment-related adverse events occurred in 5.8% and 9.1% of patients, respectively. Treatment-related adverse events led to dose reductions in 20.8% of patients in the datopotamab deruxtecan arm and 30.2% of patients in the single-agent chemotherapy arm and led to dose interruptions in 11.9% and 24.5% of patients, respectively. Treatment discontinuation due to treatment-related adverse events occurred in 2.5% of patients in the datopotamab deruxtecan arm and 2.6% of patients in the single-agent chemotherapy arm. No fatal treatment-related adverse events were reported in the datopotamab deruxtecan arm. 

As Dr Bardia et al concluded, “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.” 

“Dato-DXd is on track to be the third active antibody-drug conjugate for use in breast cancer,” added Journal of Clinical Oncology Associate Editor Gini Fleming, MD, the University of Chicago, Chicago, Illinois.

Source: 

Bardia A, Jhaveri K, Im SA, et al. 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. J Clin Oncol. Published online: September 12, 2024. doi: 10.1200/JCO.24.00920