S17 Ep12: ADCs Change Treatment Paradigms and Challenge Standard AE Management Protocols in TNBC: With Sara Nunnery, MD, MSCI; and Irene Morae Kang, MD

Breast Cancer Briefing, hosted by Sara Nunnery, MD, MSCI, a breast medical oncologist and the director of Breast Cancer Research at Tennessee Oncology in Nashville, is a podcast series that breaks down the latest news in breast cancer research, one conversation at a time.In part 2 of this conversation, filmed live onsite at the 43rd Annual Miami Breast Cancer Conference, Dr Nunnery sat down with Irene Morae Kang, MD, an assistant professor in the Department of Medical Oncology & Therapeutics Research and the medical director of Women’s Health Medical Oncology at City of Hope Orange County in Irvine, California.Their discussion focuses on the rapidly evolving treatment paradigm for first-line metastatic triple-negative breast cancer (TNBC), including the emergence of new data that is shifting standards of care. Dr Kang explained that TNBC is defined by the absence of estrogen, progesterone, and HER2 receptors, which historically restricted treatment options to non-targeted chemotherapy. A primary focus of the conversation was the role of PD-L1 expression and the use of immunotherapy. Dr Kang described PD-L1 as a checkpoint inhibitor protein on cancer cells that shuts off the immune system. By blocking this protein, oncologists can keep the body’s T-cells vigilant to fight the cancer. However, she noted that immunotherapy is typically reserved for the approximately 40% of patients who express PD-L1 and may be contraindicated for those with active autoimmune diseases or a history of severe immune-related toxicities.The dialogue transitioned into the use of antibody-drug conjugates (ADCs). Dr Kang reviewed data from major trials using TROP2-targeting ADCs in the first-line setting. Dr Kang emphasized the importance of using these highly effective agents early, as many patients with TNBC do not survive to receive a second line of therapy.Finally, Dr Kang highlighted the distinct toxicity profiles and administration schedules that guide clinical decision-making. Although sacituzumab govitecan-hziy (Trodelvy) is frequently associated with neutropenia and alopecia, the primary toxicities associated with datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) are stomatitis and ocular adverse effects like dry eye. Using Dato-DXd in practice requires a rigorous prophylactic regimen, including steroid mouthwash and lubricating eye drops. Ultimately, Dr Kang noted that because efficacy appears similar between the 2 ADCs, the choice often rests on the patient’s lifestyle, their ability to adhere to preventative AE protocols, and infusion schedule preference.