First-Line ADC Options in Metastatic Triple-Negative Breast Cancer

This segment reviews emerging first-line treatment strategies for metastatic triple-negative breast cancer (TNBC), focusing on recent trials evaluating ADCs for patients with PD-L1–negative disease. Studies such as ASCENT-03 and TROPION-Breast02 have demonstrated meaningful improvements in PFS when sacituzumab govitecan (SG) or datopotamab deruxtecan (Dato-DXd) are used in the first-line setting. An overall survival benefit has been observed with Dato-DXd, while interpretation of survival outcomes for SG may be limited by ethically appropriate crossover designs.

Given broadly similar efficacy across agents, treatment selection is driven largely by differences in toxicity profiles, dosing schedules, and patient-specific factors. Dato-DXd, administered every 3 weeks, is associated with lower rates of alopecia and neuropathy but requires proactive management of unique toxicities, including stomatitis and ocular complications. Preventive strategies such as steroid mouthwash, preservative-free eye drops, avoidance of contact lenses, and baseline ophthalmologic evaluation are essential for safe use.

In contrast, SG is associated with neutropenia and diarrhea, often requiring prophylactic growth factor support and antidiarrheal therapy. Updated prescribing guidance recommends a more proactive approach to granulocyte colony-stimulating factor use, although insurance coverage and logistical barriers may complicate implementation.

The discussion highlights that both agents produce clinically meaningful and sometimes rapid responses, even in high-risk populations such as those with short disease-free intervals. Overall, ADCs are becoming increasingly central to first-line management of metastatic TNBC, with regimen selection individualized based on tolerability, access, and patient preferences rather than major differences in efficacy.