Sacituzumab govitecan in HR-positive/HER2-negative endocrine-resistant metastatic breast cancer

Standard of care for HR-positive/HER2-negative endocrine-resistant metastatic breast cancer is sequential single-agent chemotherapy. This treatment has poor outcomes. Sacituzumab govitecan (SG) is an antibody-drug conjugate with a SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer. A multinational phase 3 study compared SG with physician’s choice of chemotherapy (eribuline, vinorelbine, capecitabine, or gemcitabine) for endocrine-resistant, chemotherapy-treated HR+/HER2- locally recurrent inoperable or metastatic breast cancer. The primary endpoint was centrally reviewed PFS. At the first planned interim analysis the median PFS was 5.5 months with SG versus 4.0 months with chemotherapy (HR 0.66; p=0.0003). Overall survival data were not yet mature. Key grade ≥ 3 treatment-related adverse events (SG versus chemotherapy) were neutropenia (51% versus 38%) and diarrhea (9% versus 1%). The authors conclude that SG demonstrated statistically significant PFS benefit over chemotherapy, with a manageable safety profile in patients with heavily pretreated, endocrine-resistant HR+/HER2- advanced breast cancer and limited treatment options.