Dr Huppert on Sequential Treatment with T-DXd and Sacituzumab Govitecan in HER2-Low Breast Cancer

Laura A. Huppert, MD, breast medical oncologist, assistant professor, University of California, San Francisco School of Medicine, discusses the impact of sequential treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) and sacituzumab govitecan-hziy (Trodelvy) on outcomes in patients with HER2-low metastatic breast cancer, according to findings from a retrospective analysis.

A multicenter cohort study was conducted to assess the efficacy and safety of these antibody-drug conjugates (ADCs) when used in sequence in a real-world setting. Patients with hormone receptor (HR)–positive or HR-negative, HER2-low breast cancer who had received both T-DXd and sacituzumab govitecan as single agents between 2020 and 2023 were enrolled onto the study. Patients may have received the agents in either order, with or without intervening therapies. A total of 84 patients were included in the analysis, 56 of whom had HR-positive, HER2-low disease.

In the HR-positive cohort, 42.9% of patients received sacituzumab govitecan before T-DXd, Huppert states. These patients had a median of 3 prior lines of therapy (range, 0-9), including 2 prior lines of chemotherapy (range, 0-5), Huppert details. The median real-world progression-free survival in this cohort was 8.0 months with sacituzumab govitecan as the first ADC administered in the sequence and 3.7 months with T-DXd as the second ADC, she reports. The median overall survival was 22.8 months with sacituzumab govitecan and 7.8 months with T-DXd, Huppert adds. Notably, the real-world median PFS and OS with T-DXd followed by sacituzumab govitecan were undetermined in patients with HR-negative disease.

Generally, investigators expect that patients will spend a shorter time on treatment with the second ADC compared with the first, especially as patients progress through lines of treatment, Huppert continues. Although most patients in this study responded longer to their first ADC, some experienced a longer duration of response on their second therapy, she notes. This finding underscores the importance of understanding the mechanisms of resistance and predictors of response with these agents, Huppert explains. Accordingly, both ADCs should be utilized in clinic, as patients can have varying responses to different therapies, and predicting individual outcomes with each agent remains a challenge, she emphasizes. Overall, these data emphasize the need for continued research into the factors influencing responses to ADCs in breast cancer and the potential benefits of sequential ADC therapies, Huppert concludes.

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