Dr. Brufsky on the Utility of Zanidatamab in HER2+ Breast Cancer

Adam M. Brufsky, MD, PhD, FACP, professor of medicine, University of Pittsburgh School of Medicine (UPMC), associate chief, Division of Hematology/Oncology, Department of Medicine, medical director, Magee-Women’s Cancer Program of UPMC Hillman Cancer Center, associate director of Clinical Investigations, UPMC Hillman Cancer Center, codirector, Comprehensive Breast Cancer Center, discusses the unique mechanism of action of zanidatamab and encouraging efficacy observed in patients with HER2-positive breast cancer.

Zanidatamab is an interesting antibody that binds to 2 separate epitope regions on the HER2 molecule, Brufsky says. The agent clusters the receptors together, leading to more inhibition in the growth of cells and potentially causing more antibody-dependent cytotoxicity, which is immune cell destruction of the HER2-positive cells, Brufsky explains.

Part 3 of the phase 1 ZWI-ZW25-101 trial (NCT02892123) investigated the addition of zanidatamab to single-agent chemotherapy in heavily pretreated patients with HER2-positive breast cancer. Although the enrolled patients were pretreated, encouraging response rates to all agents were observed, Brufsky says. Specifically, zanidatamab plus paclitaxel induced an overall response rate (ORR) of 50%, Brufsky notes. Additionally, zanidatamab plus vinorelbine resulted in an ORR of 27.3%, and zanidatamab plus capecitabine yielded an ORR of 42.9%. 

Furthermore, the ORR to all chemotherapies was 36.4%, the clinical benefit rate was 54.5%, and duration of response ranged from 1.6 months to 22.1 months, Brufsky concludes.