Dr Foldi on T-DXd and Sacituzumab Govitecan in Metastatic Breast Cancer

Julia Foldi, MD, PhD, assistant professor of medicine, Hematology/Oncology, Department of Medicine, University of Pittsburg Medical Center (UPMC), breast medical oncologist, UPMC Hillman Cancer Center, discusses the utility of of antibody-drug conjugates (ADCs), such as fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) and sacituzumab govitecan-hziy (Trodelvy), in the treatment of patients with metastatic HER2-low and triple-negative breast cancer (TNBC).

In both the HER2-low triple-negative and hormone receptor (HR)–positive metastatic breast cancer settings, there are notable data from the phase 3 DESTINY-Breast04 trial (NCT03734029)demonstrating the efficacy of T-DXd following 1 line of chemotherapy, Foldi begins. Based on the findings from this randomized, 2-arm, open-label, multicenter trial the FDA approved treatment with T-DXd for patients with unresectable or metastatic HER2-low breast cancer, in August 2022. It was noted that the study enrolled patients irrespective of HR status.

Furthermore, Foldi continues by stating that the data readout of the phase 3 DESTINY-Breast06 trial(NCT04494425) at the 2024 ASCO Annual Meeting was highly anticipated. Findings from the trial may support the replacement of chemotherapy with T-DXd in patients with endocrine-resistant HR-positive metastatic breast cancer. At the meeting, investigators reported that treatment with T-DXd elicited a statistically significant and clinically meaningful improvement in progression-free survival vs chemotherapy in pretreated patients with HR-positive, HER2-low metastatic breast cancer. Despite the risk of interstitial lung disease (ILD) that may occur with T-DXd treatment, an increase in surveillance and patient education can help minimize the risk of pulmonary toxicity.

Similarly, for treatment with sacituzumab govitecan, there are data to suggest that this ADC is better than the single-agent sequential chemotherapy for patients with TNBC who have progressed on first-line chemotherapy, Foldi expands. Although toxicities with these agents may present a challenge, they can also be managed. Foldi concludes by stating that oncologists are getting increasingly better at treating these events, ensuring that patients can stay on schedule with their treatments.