Introduction: Addressing the Unmet Need in Advanced TNBC
Triple-negative breast cancer (TNBC) remains one of the most challenging subtypes of breast cancer to treat due to its aggressive clinical course, high metastatic potential, and the lack of estrogen, progesterone, and HER2 receptor expression. For patients with programmed death ligand 1 (PD-L1)-positive advanced disease, the current standard of care has traditionally involved the combination of immune checkpoint inhibitors, such as pembrolizumab, with conventional chemotherapy. However, despite improvements in outcomes, many patients experience disease progression, necessitating more effective first-line therapeutic strategies.
The emergence of antibody-drug conjugates (ADCs) has revolutionized the treatment landscape of TNBC. Sacituzumab govitecan, an ADC targeting Trop-2—a protein highly expressed in TNBC—delivers a potent topoisomerase I inhibitor (SN-38) directly to tumor cells. Following its success in pre-treated metastatic settings, the ASCENT-04/KEYNOTE-D19 trial sought to evaluate whether replacing standard chemotherapy with sacituzumab govitecan in combination with pembrolizumab could improve outcomes for treatment-naive patients with PD-L1-positive advanced TNBC.