Dr. Kalinsky on the Evolving Treatment Landscape and Sequencing ADCs in TNBC

Kevin Kalinsky, MD, MS, associate professor, the Department of Hematology and Medical Oncology, Emory University School of Medicine, director, the Glenn Family Breast Center, Breast Medical Oncology, Louisa and Rand Glenn Family Chair in Breast Cancer Research, Winship Cancer Institute of Emory University, discusses the evolving treatment landscape for patients with triple-negative breast cancer (TNBC) and how to best sequence antibody-drug conjugates (ADCs) within this population.

Recent treatment advances have been made for patients with TNBC, specifically in those with PD-L1–positive tumors, Kalinsky begins. Patients with PD-L1-positive tumors account for approximately 40% of the TNBC population, and these patients are treated with chemotherapy and immunotherapy with pembrolizumab (Keytruda), Kalinsky says.

Additionally within the TNBC space, the ADC sacituzumab govitecan-hziy (Trodelvy) is approved by the FDA for use in patients with locally advanced or metastatic disease who have previously received 2 or more systemic therapies, including at least 1 in the metastatic setting. Patients with TNBC harboring germline BRCA mutations can also be treated with PARP inhibitors, Kalinsky continues.

For patients who have unresectable or metastatic HER2-low breast cancer, fam-trastuzumab deruxtecan-nxki (Enhertu) is an available treatment option. The emergence of trastuzumab deruxtecan for patients with metastatic HER2-low disease has represented one of the biggest advancements in the breast cancer space, Kalinsky notes. HER2-low is defined as 1+ or 2+ based upon immunohistochemistry and being gene non-amplified, Kalinsky continues. Within the phase 3 DESTINY-Breast04 trial (NCT03734029) that led to the approval of trastuzumab deruxtecan for patients with HER2-low breast cancer, a benefit was also observed with the ADC in a subset of patients with TNBC, Kalinsky explains.

Given the vast array of treatment options available for patients with TNBC, it is important to consider how to best sequence these approaches, specifically regarding the ADCs, Kalinsky emphasizes. Given that sacituzumab govitecan was approved and showed an overall survival benefit specifically in patients with TNBC, this tends to be the preferred initial ADC given to these patients, Kalinsky concludes.