Dr. Tolaney on the Efficacy of Zanidatamab Plus Chemo in HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women's Cancers, associate director, Susan F. Smith Center for Women's Cancers, senior physician, Dana-Farber Cancer Institute, associate professor of Medicine, Harvard Medical School, sheds light on zanidatamab and the data reported with the agent in combination with chemotherapy for the treatment of patients with HER2-positive breast cancer. 

Zanidatamab is a bispecific antibody that targets 2 different epitopes on the HER2 receptor, Tolaney says. The agent causes receptor clustering, which leads to downregulation of HER2, the inhibition of HER2 growth factor signaling, and the enhancement of antibody-dependent cell cytotoxicity, Tolaney explains.

Zanidatamab has always been an intriguing option, according to Tolaney. Prior data showed that the use of pertuzumab (Perjeta) or trastuzumab (Herceptin) as single agents resulted in low activity, whereas zanidatamab monotherapy demonstrated a higher level of activity, Tolaney adds.

Findings from the phase 1 ZWI-ZW25-101 trial (NCT02892123), which examined zanidatamab in combination with various chemotherapy agents, were presented during the 2021 San Antonio Breast Cancer Symposium. Results showed that the combination produced a robust overall response rate of 36.4% and a median progression-free survival of 7.3 months, Tolaney says. Notably, patients on the trial were heavily pretreated, with prior therapies including trastuzumab, pertuzumab, ado-trastuzumab emtansine (Kadcyla; T-DM1), and some TKIs, Tolaney notes.

More information on zanidatamab are anticipated in the future, and novel efforts will continue to consider bispecific targeting in HER2-positive breast cancer, Tolaney concludes.