Dr Anderson on the Evolution of ADCs in Metastatic Breast Cancer

Karen S. Anderson, MD, PhD, medical oncologist, Mayo Clinic Comprehensive Cancer Center, discusses the evolution of antibody-drug conjugates (ADCs) in the treatment of different subgroups of patients with metastatic breast cancer.

Sacituzumab govitecan-hziy (Trodelvy) has a well-established role in the second- and third-line treatment of patients with metastatic triple-negative breast cancer, Anderson says. Additionally, in February 2023, the FDA approved the ADC for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor (HR)–positive, HER2-negative breast cancer who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting.

Fam-trastuzumab deruxtecan-nxki (Enhertu) displayed benefits for patients with metastatic HER2-low breast cancer who had HR-positive or -negative tumors in the phase 3 DESTINY-Breast04 (NCT03734029) trial. Trastuzumab deruxtecan is now approved by the FDA for the treatment of select patients with HER2-positive breast cancer after previously receiving approval in the HER2-positive space. With the efficacy displayed by the ADC in patients with HER2-low disease, additional work is being conducted to improve the detection of HER2-low tumors, Anderson notes, adding that HER2-low could potentially represent half of this patient population. However, HER2-low remains difficult to measure due to variability in the testing, Anderson notes.

Since trastuzumab deruxtecan and sacituzumab govitecan are both potentially options for some patients with metastatic breast cancer, determining how to sequence these ADCs remains an important task, Anderson continues. Other investigations are examining novel ADCs and emerging targets, Anderson adds.

With the ADCS that have already been approved and the other agents coming down the pipeline, their continued emergence could move the use of chemotherapy further down the list in terms of prioritization of therapeutic approaches, Anderson concludes.