e15143 Background: Sacituzumab govitecan (SG) is an antibody-drug conjugate approved for advanced triple-negative and HR+/HER2- breast cancer. Its drug, SN-38, is metabolized by UGT1A1. Although some studies suggest higher toxicity in patients carrying the UGT1A1*28 allele, evidence on the impact of UGT1A1 variants on dose management and treatment exposure remains limited. We explored SG safety and tolerability according to UGT1A1 genotype. Methods: We conduct a single-center retrospective observational study of patients with advanced breast cancer treated with SG. Patients are grouped as Normal-Group (NG) (*1/*1) or Risk-Group(RG) (carriers of *28 allele: *1/*28 or *28/*28). In the present analysis we present the data of the first patients included regarding dose reductions due to toxicity, severe adverse events (≥Grade(G)3; CTCAE v5.0), G2, treatment exposure (number of cycles) and Grow-Colony Stimulating Factor (G-CSF) use. Categorical variables were compared using Fisher's exact tests (two sides) and continuous variables using the Mann-Whitney U test (exact two-sided p value). Results: Since June 2025 till beginning January 2026, 17 patients were included (NG n=8; RG n=9). Median age was 48 and 55 years in NG and RG respectively, rest of baseline characteristics were broadly comparable between groups (Table). Dose reductions due to toxicity occurred more frequently in the RG 66.7% vs 37.5 in the NG. Treatment exposure was numerically lower among RG with mean rank number of cycles 6.81 vs 10.19 in the NG. Rates of any ≥G3 toxicity were 44.4% vs 28.6%, ≥G3 neutropenia 33.3% vs 28.6%, and any ≥G2 toxicity 44.4% vs 42.9% respectively for the RG and NG. High G-CSF use was observed in both cohorts (RG 88.9% and NG 83.3%). Conclusions: The presence of the UGT1A1*28 polymorphism in patients treated with SG in our population is associated with frequent toxicity-related dose reductions, lower treatment exposure, and higher rates of ≥G3 toxicities, including ≥G3 neutropenia (although a high use of G-CSF was observed). This study is ongoing, and additional patients are needed to clarify the clinical utility of proactive UGT1A1 genotyping for optimal SG management. Clinical characteristics and UGT polymorphism. UGT1A1 Normal (*1/*1) Risk (*28) p-value ECOG Asymptomatic (0) 7 (87.5%) 4 (44.4%) 0.131 Symptomatic (≥1) 1 (12.5%) 5 (55.6%) Hepatic Metastases No 2 (25.0%) 3 (33.3%) 1.000 Yes 6 (75.0%) 6 (66.7%) Tumoral Burden (n. of metastatic sites) < 3 metastatic sites 4 (50.0%) 5 (55.6%) 1.000 ≥ 3 metastatic sites 4 (50.0%) 4 (44.4%) SG* Line therapy Early (2nd-3rd line) 6 (75.0%) 7 (77.8%) 1.000 Late (≥4th line) 2 (25.0%) 2 (22.2%) HER2 Status HER2-0 (Neg) 3 (37.5%) 5 (55.6%) 0.637 HER2-Low 5 (62.5%) 4 (44.4%)
Blancas et al. (Thu,) studied this question.