Dr Montero on Unmet Treatment Needs for HER2+ Metastatic Breast Cancer

“We need newer treatments that are more effective, particularly for when one of the currently approved HER2-targeted drugs stops working.”

Alberto Montero, MD, MBA, CPHQ, clinical director, Breast Cancer Medical Oncology Program, University Hospitals Seidman Cancer Center; associate professor, medicine, Case Western Reserve University School of Medicine, discusses unmet treatment needs for patients with HER2-positive metastatic breast cancer.

Chemotherapy is a hallmark of the current HER2-positive metastatic breast cancer treatment paradigm, which lacks agents that are not associated with significant toxicities, Montero says. Furthermore, although patients with this disease have several treatment options, the disease is incurable, according to Montero. Future research should focus on developing novel therapies that are effective for patients whose disease has progressed on prior lines of HER2-targeted therapy, he emphasizes.

Notably, at the 2024 San Antonio Breast Cancer Symposium, Montero and colleagues presented data from a 2-part, open-label, multicenter phase 1b/2 study (NCT05027139) investigating zanidatamab-hrii (Ziihera), a dual HER2-expressing bispecific antibody, plus the high-affinity CD47 blocker evorpacept in patients with previously treated, unresectable, locally advanced and/or metastatic HER2-expressing breast cancer and other cancers.

Patients eligible for enrollment in this trial needed to have an ECOG performance status of 0 or 1; those with treated, stable brain metastases were permitted to enroll. Cohort 1 (n = 21) included patients with HER2-positive breast cancer who had received at least 3 prior regimens, including trastuzumab (Herceptin), pertuzumab (Perjeta), and 1 of the following: ado-trastuzumab emtansine (Kadcyla), tucatinib (Tukysa), or fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu). Cohort 2 (n = 15) enrolled patients with HER2-low breast cancer that had never been HER2 positive who had received at least 2 prior regimens; prior treatment with T-DXd was allowed. Cohort 3 (n = 8) enrolled patients with HER2-positive gastroesophageal adenocarcinoma or other HER2-overexpressing non-breast cancers. In part b of the trial, patients in the expansion cohorts received the combination at the recommended phase 2 dose of 1200 mg/less than 70 kg or 1600 mg/70 kg or greater of zanidatamab plus 30 mg/kg of evorpacept every 2 weeks of each 28-day cycle.