On January 17, 2025, the US Food and Drug Administration (FDA) approved datapotamab deruxtecan-dlnk (Dato-DXd), a TROP2-directed antibody-drug conjugate (ADC), for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
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This approval is based on the results of the TROPION-Breast01 study, a multicenter, open-label, randomized trial evaluating the efficacy of Dato-DXd in patients with disease progression who were no longer suitable for endocrine therapy. Eligible participants had received one or two prior lines of chemotherapy for unresectable or metastatic disease. Patients with a history of interstitial lung disease (ILD), ongoing ILD, clinically active brain metastases, or significant corneal disease were excluded. The trial also excluded patients with an Eastern Cooperative Oncology Group (ECOG) performance status greater than 1.
A total of 732 patients were randomized 1:1 to receive either Dato-DXd (n=365) or the investigator’s choice of chemotherapy (n=367), which included eribulin, capecitabine, vinorelbine, or gemcitabine. The study’s primary efficacy measures were progression-free survival (PFS), assessed by blinded independent central review (BICR) based on RECIST v1.1 criteria, and overall survival (OS). Additional endpoints included confirmed objective response rate (ORR) and duration of response (DOR).
Results showed that the median PFS was 6.9 months in the Dato-DXd arm compared to 4.9 months in the chemotherapy group, with a hazard ratio of 0.63 (95% CI: 0.52, 0.76; p<0.0001). However, the median OS was similar between the two arms, at 18.6 months for Dato-DXd and 18.3 months for chemotherapy, with no statistically significant difference (hazard ratio 1.01; 95% CI: 0.83, 1.22). Confirmed ORR was 36% in the Dato-DXd group compared to 23% in the chemotherapy arm, while median DOR was 6.7 months and 5.7 months, respectively.
The most common adverse reactions observed in ≥20% of patients included stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, and alopecia, to name a few.
The approval of Dato-DXd provides a new treatment option for patients with advanced HR-positive, HER2-negative breast cancer who have progressed on previous therapies. The results from the TROPION-Breast01 trial demonstrate improved progression-free survival compared to chemotherapy, offering new hope for patients battling this challenging disease.
References:
“FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer,” U.S. Food And Drug Administration, Jan. 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast
A. Bardia 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,” Journal of Clinical Oncology, Sep. 2024, doi: 10.1200/jco.24.00920.
Christina Fotopoulou
