Table 4.

Selected studies assessing the role of antibody-drug conjugates in the treatment of hormone receptor-positive metastatic breast cancer.

	Datopotumab-DXd TROPION-Breast01 [20]	Sacituzumab govitecan TROPiCS-02 [18]	T-DXd DESTINY Breast-04 [19]
ADC Target Payload Linker DAR Bystander effect	Trop2 Topo1 inhibitor Tumor selective, cleavable 4:1 Yes	Trop2 Topo1 inhibitor (SN38) Tumor selective, cleavable 8:1 Yes	HER2 Topo1 inhibitor Tumor selective, cleavable 7–8:1 Yes
Study population	Metastatic HR+/HER2- disease, 1–2 prior lines of chemotherapy dato vs TPC	Metastatic HR+/HER2- disease, ET + CDK4/6 → 2–4 prior lines of chemotherapy SG vs TPC	Metastatic HER2-low with 1–2 prior lines of therapy in the metastatic setting
Sample size	732 (1:1 randomization)	543 (1:1 randomization)	557 (2:1) ∼90% HR+
PFS	6.9 vs 4.9 months (HR = 0.63, p < 0.001)	5.5 vs 4 months (HR = 0.65, <0.001)	9.6 vs. 4.2 months (HR = 0.37, in HR + group)
OS	Not mature	15.5 vs. 11.2 m. (HR = 0.79, p.013)	23.9 vs 17.6 m. (.HR = 069, in HR + group)
Follow up	9.7 months	13 months	32 months
Notes	ORR 36 vs 22%. Stomatitis 50%, alopecia 36%, ILD 3%	Benefit greater in higher Trop 2 expression. Nausea/vomiting and neutropenia	Nausea/vomiting, ILD
U.S. FDA approval	No	Yes, February 2023 → at least 2 prior lines of chemotherapy in the metastatic setting	Yes, August 2022 → at least 1 prior line of chemotherapy in the metastatic setting

Abbreviations: DAR: drug to antibody ratio; DXd: deruxtecan; HER2: human epidermal growth factor receptor 2; HR: hazard ratio, HR+: hormone receptor positive; ILD: interstitial lung disease; ORR: overall response rate; OS: overall survival; PFS: progression free survival; U.S. FDA: United States Food and Drug Administration.