Impact of UGT1A1*28 Allele on the Safety and Effectiveness of Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: Real-World Evidence

Background: The UGT1A1 gene is associated with the toxicity caused by SN38, the cytotoxic component of Sacituzumab govitecan (SG) used in the treatment of metastatic triple-negative breast cancer (mTNBC), among other approved indications. In this study, we aimed to analyze the effect of UGT1A1*28 al...

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Autores: Do Pazo Oubiña, Fernando, del Rosario García, Betel, Miarons, Marta, Legido Perdices, Eva M., Prado Mel, Elena, Díaz, Ruth Ramos, Gutiérrez Nicolás, Fernando
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/26594
Acceso en línea:https://hdl.handle.net/20.500.13003/26594
Access Level:acceso abierto
Palabra clave:Sacituzumab govitecan
UGT1A1
drug toxicity
febrile neutropenia
germline mutations
triple negative breast cancer
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spelling Impact of UGT1A1*28 Allele on the Safety and Effectiveness of Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: Real-World EvidenceDo Pazo Oubiña, Fernandodel Rosario García, BetelMiarons, MartaLegido Perdices, Eva M.Prado Mel, ElenaDíaz, Ruth RamosGutiérrez Nicolás, FernandoSacituzumab govitecanUGT1A1drug toxicityfebrile neutropeniagermline mutationstriple negative breast cancerBackground: The UGT1A1 gene is associated with the toxicity caused by SN38, the cytotoxic component of Sacituzumab govitecan (SG) used in the treatment of metastatic triple-negative breast cancer (mTNBC), among other approved indications. In this study, we aimed to analyze the effect of UGT1A1*28 allele on the safety and, secondarily, the effectiveness of SG in mTNBC. Methods: This was a multicenter, ambispective study that included patients treated with SG for mTNBC. Genotyping for UGT1A1*28 was performed using real-time polymerase chain reaction (PCR). Adverse events (AEs) of grade ≥ 2 during the first three cycles were compared between patients who were homozygous mutant (UGT1A1*28/*28) and those with wild-type (WT) or heterozygous genotypes. Effectiveness between the two groups was also compared using progression-free survival (PFS) and overall survival (OS) assessed with the Kaplan–Meier method. Results: A total of 81 patients were included: 37.0% were WT, 55.6% heterozygous, and 7.4% homozygous mutant. All UGT1A1 *28/*28 patients experienced grade ≥ 2 AEs (100% vs. 69.3%; p = 0.109), with a statistically significant association in the case of febrile neutropenia (33.3% vs. 6.7%; p = 0.025), and a trend towards higher rates of anemia and diarrhea (50.0% vs. 17.3%; p = 0.053). Genotype did not influence PFS or OS; however, dose reductions were associated with better survival outcomes. Conclusions: This real-world study shows a correlation between toxicity and the presence of the UGT1A1*28 mutation in patients treated with SG for mTNBC. Improving treatment tolerability through dose reductions may enhance SG effectiveness. These findings support the implementation of UGT1A1 genotyping in routine clinical practice.MDPI AG20262026-01-1020262026-01-10research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/26594reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/265942026-06-22T12:44:07Z
dc.title.none.fl_str_mv Impact of UGT1A1*28 Allele on the Safety and Effectiveness of Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: Real-World Evidence
title Impact of UGT1A1*28 Allele on the Safety and Effectiveness of Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: Real-World Evidence
spellingShingle Impact of UGT1A1*28 Allele on the Safety and Effectiveness of Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: Real-World Evidence
Do Pazo Oubiña, Fernando
Sacituzumab govitecan
UGT1A1
drug toxicity
febrile neutropenia
germline mutations
triple negative breast cancer
title_short Impact of UGT1A1*28 Allele on the Safety and Effectiveness of Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: Real-World Evidence
title_full Impact of UGT1A1*28 Allele on the Safety and Effectiveness of Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: Real-World Evidence
title_fullStr Impact of UGT1A1*28 Allele on the Safety and Effectiveness of Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: Real-World Evidence
title_full_unstemmed Impact of UGT1A1*28 Allele on the Safety and Effectiveness of Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: Real-World Evidence
title_sort Impact of UGT1A1*28 Allele on the Safety and Effectiveness of Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: Real-World Evidence
dc.creator.none.fl_str_mv Do Pazo Oubiña, Fernando
del Rosario García, Betel
Miarons, Marta
Legido Perdices, Eva M.
Prado Mel, Elena
Díaz, Ruth Ramos
Gutiérrez Nicolás, Fernando
author Do Pazo Oubiña, Fernando
author_facet Do Pazo Oubiña, Fernando
del Rosario García, Betel
Miarons, Marta
Legido Perdices, Eva M.
Prado Mel, Elena
Díaz, Ruth Ramos
Gutiérrez Nicolás, Fernando
author_role author
author2 del Rosario García, Betel
Miarons, Marta
Legido Perdices, Eva M.
Prado Mel, Elena
Díaz, Ruth Ramos
Gutiérrez Nicolás, Fernando
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Sacituzumab govitecan
UGT1A1
drug toxicity
febrile neutropenia
germline mutations
triple negative breast cancer
topic Sacituzumab govitecan
UGT1A1
drug toxicity
febrile neutropenia
germline mutations
triple negative breast cancer
description Background: The UGT1A1 gene is associated with the toxicity caused by SN38, the cytotoxic component of Sacituzumab govitecan (SG) used in the treatment of metastatic triple-negative breast cancer (mTNBC), among other approved indications. In this study, we aimed to analyze the effect of UGT1A1*28 allele on the safety and, secondarily, the effectiveness of SG in mTNBC. Methods: This was a multicenter, ambispective study that included patients treated with SG for mTNBC. Genotyping for UGT1A1*28 was performed using real-time polymerase chain reaction (PCR). Adverse events (AEs) of grade ≥ 2 during the first three cycles were compared between patients who were homozygous mutant (UGT1A1*28/*28) and those with wild-type (WT) or heterozygous genotypes. Effectiveness between the two groups was also compared using progression-free survival (PFS) and overall survival (OS) assessed with the Kaplan–Meier method. Results: A total of 81 patients were included: 37.0% were WT, 55.6% heterozygous, and 7.4% homozygous mutant. All UGT1A1 *28/*28 patients experienced grade ≥ 2 AEs (100% vs. 69.3%; p = 0.109), with a statistically significant association in the case of febrile neutropenia (33.3% vs. 6.7%; p = 0.025), and a trend towards higher rates of anemia and diarrhea (50.0% vs. 17.3%; p = 0.053). Genotype did not influence PFS or OS; however, dose reductions were associated with better survival outcomes. Conclusions: This real-world study shows a correlation between toxicity and the presence of the UGT1A1*28 mutation in patients treated with SG for mTNBC. Improving treatment tolerability through dose reductions may enhance SG effectiveness. These findings support the implementation of UGT1A1 genotyping in routine clinical practice.
publishDate 2026
dc.date.none.fl_str_mv 2026
2026-01-10
2026
2026-01-10
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/26594
url https://hdl.handle.net/20.500.13003/26594
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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