S18 Ep35: The ADC Revolution in Metastatic Breast Cancer: Redefining Treatment Selection and Sequencing

Antibody-drug conjugates (ADCs) have transformed the treatment landscape for metastatic triple-negative breast cancer, offering new first-line options for patients with limited alternatives. Clinical data for agents like sacituzumab govitecan and datopotamab deruxtecan demonstrate significant improvements in progression-free survival, though clinicians must navigate distinct toxicity profiles, including neutropenia, diarrhea, and ocular surface events. In PD-L1 positive disease, combining ADCs with checkpoint inhibitors like pembrolizumab leverages potential synergistic effects to improve outcomes. However, optimal sequencing remains a critical challenge, particularly in the absence of prospective data for patients progressing after prior immunotherapy. Clinical decision-making requires balancing biomarker status, such as BRCA mutations and PD-L1 expression, with patient-specific factors like symptom burden and the need for rapid response. While ADCs provide potent therapeutic alternatives, the field currently lacks definitive guidelines for managing sequential therapy or re-challenging with immunotherapy in recurrent cases.