Dr Tarantino on the Use of ADCs in HR+ Breast Cancer

Paolo Tarantino, MD, researcher, the European Institute of Oncology, clinical research fellow, Dana-Farber Cancer Institute, discusses the use of antibody drug conjugates (ADCs) in patients with hormone receptor (HR)–positive breast cancer.

In an OncLive® State of the Science Summit™, Tarantino and colleagues from Dana-Farber Cancer Institute each gave presentations on topics spanning breast cancer treatment. In his presentation, Tarantino reviewed the expanding arsenal of drugs that are being developed beyond endocrine treatment for patients with HR-positive metastatic breast cancer. Metastatic HR-positive breast cancer still stands as the most common subtype of breast cancer, and for many years, the mainstay of treatment for this patient population has been traditional chemotherapy, Tarantino emphasizes. Although many different agents are used in this setting, a major shift that occurred in recent years was the development of more selective chemotherapies, such as ADCs, Tarantino explains. ADCs are complex molecules that aim to deliver chemotherapy through the engaging of an antigen present on tumor cells, Tarantino notes. Two ADCs have been FDA approved for patients with metastatic HR-positive breast cancer: fam-trastuzumab deruxtecan-nxki (Enhertu) and sacituzumab govitecan-hziy (Trodelvy).

Both these FDA-approved agents have improved overall survival (OS) and progression-free survival (PFS) in patients with pretreated HR-positive metastatic breast cancer, he expands. For example, in the phase 3 DESTINY-Breast04 trial (NCT03734029), trastuzumab deruxtecan led to major improvements in PFS and OS vs physician’s choice of chemotherapy in patients with previously treated HR-positive, HER2-low metastatic breast cancer, he says.

Sequencing trastuzumab deruxtecan and sacituzumab govitecan remains a challenge, Tarantino continues. Currently, investigators are unsure of the activity of these 2 agents in sequence, he notes. The most effective sequence investigated thus far has been trastuzumab deruxtecan first, followed by sacituzumab govitecan, he says. Overall, ADCs continue to reshape the HR-positive breast cancer field, and trastuzumab deruxtecan and sacituzumab govitecan are the frontrunners in a wave of ADCs that will arrive in this setting, Tarantino concludes.