Dr Phadke on Sequencing ADCs in HR+/HER2– Breast Cancer

Sneha Phadke, DO, MPH, clinical associate professor, Department of Internal Medicine, Program 4: Cancer Epidemiology and Population Science, associate member, University of Iowa, Holden Comprehensive Cancer Center, discusses sequencing treatment with antibody drug conjugates (ADCs) in hormone receptor (HR)–positive/HER2-negative breast cancer, as well as questions remaining within this space.

In an OncLive® State of the Science Summit™, Phadke and colleagues from the Holden Comprehensive Cancer Center each gave presentations on topics spanning breast cancer treatment. Regarding the use of ADCs, Phadke shares that there are 2 specific ADCs that she would initially reach for in this patient population: sacituzumab govitecan-hziy (Trodelvy) and fam-trastuzumab deruxtecan-nxki (Enhertu). Both ADCs have a similar cytotoxic payload and are topoisomerase 1 inhibitor chemotherapies, which is are a specific class of agents designed to disrupt DNA replication in cancer cells, Phadke says. However, there remains some concern about the potential development of cross resistance with the use of these agents, Phadke adds. If a patient is treated with 1 of these 2 ADCs, the efficacy of subsequent treatment with a different ADC is still unknown, Phadke emphasizes. Additional data are needed to better understand whether cross resistance should be a concern for these patients.

However, The first-in-human phase 1 TROPION-PanTumor01 trial (NCT03401385) is currently evaluating the Trop-2–targeting ADC datopotamab deruxtecan (Dato-DXd; DS-1062a) in patients with solid tumors, including those with non–small cell lung cancer, metastatic triple-negative breast cancer, and HR-positive/HER2-negative breast cancer. In this evaluation, Findings from the phase 1 study showed that the overall response rate was higher in patients who had not previously received a topoisomerase 1 inhibitor, Phadke expands. These data indicate that these patients likely experienced cross resistance, Phadke states.

However, minimal data exist to guide the optimal sequencing of these ADCs, Phadke says. Depending on a given patient’s individual patient factors, it may be reasonable to consider using both agents, Phadke concludes.