Sacituzumab Govitecan in HER2-Low Disease

The patient receives T-DXd and experiences partial response at 3 months. After 2.5 years of treatment, she reports new abdominal pain accompanied by nausea and vomiting. She is admitted for SBO, and imaging confirms disease progression with new metastases to the lymph nodes, abdomen, and liver. SG is initiated as third-line (3L) treatment.

SG targets TROP2, which is expressed in 80% to 90% of TNBCs. FDA approval of SG in mTNBC was supported by the randomized phase 3 ASCENT trial (N=529) in a more heavily pretreated population (~70% 2-3 lines, ~30% >3). Post-hoc analysis of the HER2-low subgroup revealed a 48% reduced risk for death and 53% reduced risk for disease progression versus physician’s choice of chemotherapy (capecitabine, eribulin, vinorelbine, or gemcitabine). ORR was 32%.

SG-related AEs include neutropenia (63%; Grade 3+, 52%) and febrile neutropenia (6%, 6%); granulocyte colony-stimulating factor (G-CSF) should be considered for secondary prophylaxis. Other events include diarrhea (65%, Grade 3+, 12%), nausea (62%, 3%), fatigue (52%, 4%), and anemia (40%, 9%). UGT1A1*28 polymorphisms are associated with increased hematologic and gastrointestinal toxicity, and disproportionately affect Black vs White individuals. Routine testing of all patients is not currently recommended due to low incidence rates.