Dr Hamilton on the Safety Profile of ADCs in HER2-Low and -Ultralow Breast Cancer

Erika P. Hamilton, MD, director, Breast Cancer, director, Gynecologic Cancer Research, Sarah Cannon Research Institute, discusses the safety profile of antibody-drug conjugates (ADCs) in patients with hormone receptor–positive, HER2-low and -ultralow metastatic breast cancer, as well as effective prophylaxis, monitoring, and mitigation strategies for some of the toxicities associated with these agents.

All ADCs should not be grouped into a single class when considering their safety profiles, as each agent is associated with unique toxicities, Hamilton begins. For instance, key toxicities associated with the ADC sacituzumab govitecan-hziy (Trodelvy) include low blood cell counts and diarrhea, whereas patients who receive fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) may experience nausea and interstitial lung disease (ILD), Hamilton says. ILD was a particularly concerning adverse effect (AE) when T-DXd was first being evaluated in patients with breast cancer, as some cases of this AE were fatal, she notes. Approximately 10% to 15% of patients who receive T-DXd will develop ILD of any grade, according to Hamilton. However, increased ILD awareness and monitoring across the breast cancer community has significantly decreased the incidence of fatal cases of this AE, Hamilton emphasizes.

Nausea remains one of the most common AEs associated with T-DXd, Hamilton adds. In the early days of T-DXd development, many clinical trials that evaluated this agent in patients with breast cancer did not mandate the use of anti-emetics, she explains. Now, treatment guidelines published by the National Comprehensive Cancer Network, ASCO, and ESMO recommend the up-front administration of a 2- or 3-drug anti-emetic prophylactic regimen before patients receiving T-DXd experience any symptoms of nausea, Hamilton reports. She notes that anti-emetic regimens have been effective in her practice, as her patients rarely develop significant nausea following this prophylactic measure. For patients who continue to experience significant nausea related to T-DXd, Hamilton recommends administering olanzapine at night.