Optimizing Sequencing of Antibody–Drug Conjugates in Metastatic Triple-Negative Breast Cancer

The sequencing of antibody–drug conjugates (ADCs) in metastatic triple-negative breast cancer (mTNBC) is increasingly relevant as multiple therapies become available. Key differences among ADCs—including molecular targets, linker technology, and cytotoxic payloads—can influence both efficacy and tolerability. Emerging evidence from studies comparing sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-Dxd) highlights considerations for sequencing based on prior exposure, tumor biology, and potential non-cross-resistance of payloads. Clinical practice increasingly favors individualized sequencing strategies, taking into account tumor HER2 expression, prior therapies, and patient-specific factors. ADC target specificity and payload mechanism may guide clinicians toward maximizing response duration while minimizing overlapping toxicities. Overall, thoughtful sequencing of ADCs offers an opportunity to extend disease control and improve outcomes in patients with advanced TNBC.