@misc{10481/111495,
year = {2026},
month = {2},
url = {https://hdl.handle.net/10481/111495},
abstract = {Background/Objectives: Sacituzumab govitecan (SG) releases SN-38, the same active me
tabolite as irinotecan, thereby sharing key metabolic pathways and toxicity mechanisms. 
The clearance of SN-38 is strongly influenced by UGT1A1 polymorphisms, particularly 
the UGT1A1*28 allele. While UGT1A1*28 genotyping routinely guides irinotecan dosing, 
no such recommendations exist for SG. This study describes the relationship between 
UGT1A1*28 and severe SG-related toxicity in real-world practice, identifying early safety 
signals and exploring the clinical and economic impact. Methods: This retrospective ob
servational study (2021–2025) included patients with metastatic breast cancer treated with 
SG and patients with advanced gastrointestinal malignancies treated with irinotecan at a 
tertiary hospital. In the SG cohort, genotyping followed grade ≥3 toxicity; in the irinotecan 
cohort, it was performed prospectively. Toxicity (Common Terminology Criteria for Ad
verse Events version 5.0) and healthcare costs related to hospitalizations were estimated 
using official institutional tariffs. Results: All nine SG patients with severe toxicity (100%) 
carried the UGT1A1*28 allele. In the irinotecan cohort (n = 74), which was managed with 
genotype-guided dosing, severe toxicity and hospitalization were less frequent. SG was 
associated with higher mean costs per treated patient (€2817.01 vs. €1233.63), driven by 
toxicity-related admissions (33.3% vs. 10.8%). Genotyping costs (€10.51) were negligible 
compared to daily hospitalization expenses (up to €1984.90). Conclusions: Severe SG-re
lated toxicity reveals a consistent UGT1A1*28-associated vulnerability. Given the drug’s 
recent approval in Spain, these data represent an urgent real-world safety signal. The 
marked disparity between low genotyping costs and high hospitalization expenses sup
ports implementing preventive UGT1A1 testing to optimize the safety and sustainability 
of sacituzumab govitecan therapy.},
publisher = {MDPI},
keywords = {sacituzumab-govitecan},
keywords = {UGT1A1*28},
keywords = {pharmacogenetics},
title = {The Early Safety Signal of Sacituzumab Govitecan-Related Toxicity and the UGT1A1*28 Genotype in Metastatic Breast Cancer: A Real-World Preliminary Report},
doi = {10.3390/jcm15051715},
author = {Martínez Pérez, María and Nieto-Sánchez, María Teresa and Díaz Villamarín, Xando and Torres García, Alicia and Fernández Varón, Emilio and Prados-Carmona, Alvaro and Legerén, Marta and Cabeza-Barrera, José and Blancas López-Barajas, María Isabel and Morón Romero, María Rocío},
}