Dr Yuan on Intracranial Activity With T-DXd Plus Pertuzumab in HER2+ Metastatic Breast Cancer

"The study was asking a very valid question: does T-DXd have CNS efficacy? [Investigators] found that those patients [who] did not go through radiation therapy and just received systemic therapy was T-DXd saw [comparable] CNS responses. [This gives] our patients another option besides the HER2CLIMB approach."

Yuan Yuan, MD, PhD, the director of Breast Medical Oncology Medicine, the medical director of the Breast Oncology Disease Research Group, and a professor at Cedars-Sinai Medical Cente;, as well as a health sciences clinical professor at the University of California, Los Angeles, discussed the implications of data from the prospective, phase 3b/4 DESTINY-Breast12 study (NCT04739761) evaluating first-line fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta) in HER2-positive advanced/metastatic breast cancer.

The DESTINY-Breast12 study was a multicenter, single-arm, two-cohort, open-label trial enrolling patients with pathologically confirmed HER2-positive advanced or metastatic breast cancer, regardless of whether they presented with brain metastases at baseline. A core question driving the study was whether T-DXd exhibited efficacy within the central nervous system (CNS).

Findings from the study were presented during the 2024 ESMO Congress, and demonstrated that the T-DXd combination showcased considerable overall and intracranial activity. Furthermore, this activity proved to be durable in the patient population studied, specifically those with HER2-positive metastatic breast cancer who had stable and active brain metastases.

According to Yuan, these positive results are significant because they expand the available treatment options for patients, where historically, the standard of care approach included the regimen from the phase 2 HER2CLIMB (NCT02614794) regimen comprising tucatinib (Tukysa), ado-trastuzumab emtansine (Kadcyla), and capecitabine (Xeloda). Yuan concluded that the data from DESTINY-Breast12 are now giving patients another viable treatment option.