Dr Tarantino on the Impact of Emerging ADCs in HR+ Breast Cancer

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

For patients with HR-positive metastatic breast cancer, there is an expanding arsenal of drugs that are being developed beyond endocrine therapies for this patient population, Tarantino begins. For many years, the mainstay of treatment for this population has consisted of traditional chemotherapy, he says. However, the development of more selective chemotherapies, such as ADCs, has caused a shift in the treatment of this patient population, Tarantino notes. The 2 ADCs that have been approved for select patients within this subset are fam-trastuzumab deruxtecan-nxki (Enhertu) and sacituzumab govitecan-hziy (Trodelvy).

Both of these ADCs have shown an improvement in overall survival and progression-free survival in previously treated patients with HR-positive metastatic breast cancer, he expands. Both ADCs have had a major impact for patients, based on previously presented data, Tarantino says. Most recently at the 2023 ASCO Annual Meeting, updated data from the phase 3 TROPiCS-02 study (NCT03901339)—the study that supported the approval of sacituzumab govitecan for pretreated patients with HR-positive/HER2-negative breast cancer after endocrine therapy and at least 2 additional systemic therapies in the metastatic setting—showed that the ADC produced an improvement in OS vs physician’s choice of therapy, he adds.

Currently, a major challenge within this space is how to sequence these agents, Tarantino continues. Right now, trastuzumab deruxtecan is generally given first for patients who have HER2-low disease because this ADC was tested in a less pretreated patient population, he says. Contrarily, sacituzumab govitecan is utilized in later lines following a minimum of 2 lines of chemotherapy or ADCs, Tarantino emphasizes. ADCs have only just started to make their mark on this treatment space, and further research and data will continue to drive treatment decisions, Tarantino concludes.