Dr. Gradishar on the Benefit of Trastuzumab Deruxtecan in HER2+ Breast Cancer

William J. Gradishar, MD, chief of hematology and oncology, Department of Medicine; Betsy Bramsen Professorship of Breast Oncology; and a professor of medicine (hematology and oncology) at Northwestern University Feinberg School of Medicine, discusses the benefit of fam-trastuzumab deruxtecan-nxki (Enhertu; DS-8201) in patients with HER2-positive breast cancer and stable brain metastases.

In the phase 2 DESTINY-Breast01 trial, investigators evaluated trastuzumab deruxtecan in patients with HER2-positive breast cancer who received 2 or more prior HER2-directed therapies, including ado-trastuzumab emtansine (T-DM1; Kadcyla), says Gradishar. These patients had received standard treatments before enrolling on the trial. Importantly, patients could have stable brain metastases and still be included on the trial, adds Gradishar. The bulk of the trial was focused on the established dose, which was 5.4 mg/kg administered intravenously every 3 weeks.

The most compelling piece of evidence that came from the trial is the fraction of patients who responded, according to Gradishar. The data that were presented in a waterfall plot garnered a lot of attention. When looking at the forest plots, no subset of patients did not achieve benefit from trastuzumab deruxtecan.

More recently, additional data were presented at the ESMO Breast Cancer Virtual Meeting 2020, which focused on the population of patients who had stable brain metastases. While the duration of benefit was longer in patients who did not have brain metastases, it was clear patients who had stable brain metastases also benefitted from the ADC, concludes Gradishar.