Influence of the UGT1A1 gene polymorphism on treatment with sacituzumab govitecan. Narrative review

Objective: Sacituzumab govitecan is an antineoplastic therapy composed of a monoclonal antibody directed to the Trop2 antigen, conjugated to SN-38, an active metabolite of irinotecan that inhibits topoisomerase I. It is indicated for the treatment of metastatic triple-negative breast cancer in patie...

Descripción completa

Detalles Bibliográficos
Autores: Legido Perdices, Eva María, Do Pazo Oubiña, Fernando, Prado Mel, Elena, Miarons, Marta, García, Betel Del Rosario, Gutiérrez Nicolás, Fernando
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:español
OAI Identifier:oai:docusalut.com:20.500.13003/25203
Acceso en línea:https://hdl.handle.net/20.500.13003/25203
Access Level:acceso abierto
Palabra clave:Anticuerpo conjugado
Conjugated antibody
Cáncer de mama triple negativo
Polimorfismos UGT1A1
Sacituzumab govitecan
Toxicidad
Toxicity
Triple-negative breast cancer
UGT1A1 polymorphisms
id ES_1fffd0feda1efdeda15778ecff99a5dc
oai_identifier_str oai:docusalut.com:20.500.13003/25203
network_acronym_str ES
network_name_str España
repository_id_str
spelling Influence of the UGT1A1 gene polymorphism on treatment with sacituzumab govitecan. Narrative reviewLegido Perdices, Eva MaríaDo Pazo Oubiña, FernandoPrado Mel, ElenaMiarons, MartaGarcía, Betel Del RosarioGutiérrez Nicolás, FernandoAnticuerpo conjugadoConjugated antibodyCáncer de mama triple negativoPolimorfismos UGT1A1Sacituzumab govitecanToxicidadToxicityTriple-negative breast cancerUGT1A1 polymorphismsObjective: Sacituzumab govitecan is an antineoplastic therapy composed of a monoclonal antibody directed to the Trop2 antigen, conjugated to SN-38, an active metabolite of irinotecan that inhibits topoisomerase I. It is indicated for the treatment of metastatic triple-negative breast cancer in patients who have received at least two prior lines of treatment, with at least one in the metastatic context. SN-38 is eliminated by glucuronidation mediated by uridine diphosphate-glucuronosyltransferase-1A1 (UGT1A1) enzymes, present in the liver. Mutations in the UGT1A1 gene decrease the expression of these enzymes, which increases the concentration of SN-38 and, consequently, increases the toxicity of the drug, especially in the form of neutropenia and diarrhea. This study aims to analyze the relationship between UGT1A1 gene polymorphisms and toxicity associated with treatment with sacituzumab govitecan, in addition to reviewing the usefulness of genetic screening prior to starting therapy. Methods: A non-systematic literature review was conducted on the impact of UGT1A1 gene polymorphisms on the safety of sacituzumab govitecan treatment in patients with triple-negative breast cancer. The search included primary and secondary literature sources and communications from oncology conferences. Results: Patients treated with sacituzumab govitecan with the UGT1A1*28/*28 mutated genotype are more likely to experience grade more than 3 hematologic adverse events: neutropenia (approximate incidence of 60% compared to 40% for 1/*1 and 1/*28 genotypes), febrile neutropenia (18% homozygotes vs. 5% heterozygotes and 3% wild-type), grade more than 3 anemia (15% vs. 6% and 4%, respectively); as well as grade more than 3 diarrhea (24% vs. 13% and 6%, respectively). Additionally, treatment discontinuation rates are higher in *28/*28 individuals (6% compared to 1% heterozygotes and 2% wild-type). Conclusions: Patients homozygous for the UGT1A1*28 allele are at significantly increased risk of developing serious adverse events. Despite the clear relationship between UGT1A1 polymorphisms and sacituzumab-govitecan toxicity, the review suggests that there is insufficient consensus on the need for systematic genetic screening. However, the findings indicate that such screening could be useful for identifying patients at risk and personalizing sacituzumab govitecan therapy.Elsevier20252025-03-2520252025-03-25review articlehttp://purl.org/coar/resource_type/c_dcae04bcinfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/25203reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsEspañolspaopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/252032026-06-22T12:44:07Z
dc.title.none.fl_str_mv Influence of the UGT1A1 gene polymorphism on treatment with sacituzumab govitecan. Narrative review
title Influence of the UGT1A1 gene polymorphism on treatment with sacituzumab govitecan. Narrative review
spellingShingle Influence of the UGT1A1 gene polymorphism on treatment with sacituzumab govitecan. Narrative review
Legido Perdices, Eva María
Anticuerpo conjugado
Conjugated antibody
Cáncer de mama triple negativo
Polimorfismos UGT1A1
Sacituzumab govitecan
Toxicidad
Toxicity
Triple-negative breast cancer
UGT1A1 polymorphisms
title_short Influence of the UGT1A1 gene polymorphism on treatment with sacituzumab govitecan. Narrative review
title_full Influence of the UGT1A1 gene polymorphism on treatment with sacituzumab govitecan. Narrative review
title_fullStr Influence of the UGT1A1 gene polymorphism on treatment with sacituzumab govitecan. Narrative review
title_full_unstemmed Influence of the UGT1A1 gene polymorphism on treatment with sacituzumab govitecan. Narrative review
title_sort Influence of the UGT1A1 gene polymorphism on treatment with sacituzumab govitecan. Narrative review
dc.creator.none.fl_str_mv Legido Perdices, Eva María
Do Pazo Oubiña, Fernando
Prado Mel, Elena
Miarons, Marta
García, Betel Del Rosario
Gutiérrez Nicolás, Fernando
author Legido Perdices, Eva María
author_facet Legido Perdices, Eva María
Do Pazo Oubiña, Fernando
Prado Mel, Elena
Miarons, Marta
García, Betel Del Rosario
Gutiérrez Nicolás, Fernando
author_role author
author2 Do Pazo Oubiña, Fernando
Prado Mel, Elena
Miarons, Marta
García, Betel Del Rosario
Gutiérrez Nicolás, Fernando
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Anticuerpo conjugado
Conjugated antibody
Cáncer de mama triple negativo
Polimorfismos UGT1A1
Sacituzumab govitecan
Toxicidad
Toxicity
Triple-negative breast cancer
UGT1A1 polymorphisms
topic Anticuerpo conjugado
Conjugated antibody
Cáncer de mama triple negativo
Polimorfismos UGT1A1
Sacituzumab govitecan
Toxicidad
Toxicity
Triple-negative breast cancer
UGT1A1 polymorphisms
description Objective: Sacituzumab govitecan is an antineoplastic therapy composed of a monoclonal antibody directed to the Trop2 antigen, conjugated to SN-38, an active metabolite of irinotecan that inhibits topoisomerase I. It is indicated for the treatment of metastatic triple-negative breast cancer in patients who have received at least two prior lines of treatment, with at least one in the metastatic context. SN-38 is eliminated by glucuronidation mediated by uridine diphosphate-glucuronosyltransferase-1A1 (UGT1A1) enzymes, present in the liver. Mutations in the UGT1A1 gene decrease the expression of these enzymes, which increases the concentration of SN-38 and, consequently, increases the toxicity of the drug, especially in the form of neutropenia and diarrhea. This study aims to analyze the relationship between UGT1A1 gene polymorphisms and toxicity associated with treatment with sacituzumab govitecan, in addition to reviewing the usefulness of genetic screening prior to starting therapy. Methods: A non-systematic literature review was conducted on the impact of UGT1A1 gene polymorphisms on the safety of sacituzumab govitecan treatment in patients with triple-negative breast cancer. The search included primary and secondary literature sources and communications from oncology conferences. Results: Patients treated with sacituzumab govitecan with the UGT1A1*28/*28 mutated genotype are more likely to experience grade more than 3 hematologic adverse events: neutropenia (approximate incidence of 60% compared to 40% for 1/*1 and 1/*28 genotypes), febrile neutropenia (18% homozygotes vs. 5% heterozygotes and 3% wild-type), grade more than 3 anemia (15% vs. 6% and 4%, respectively); as well as grade more than 3 diarrhea (24% vs. 13% and 6%, respectively). Additionally, treatment discontinuation rates are higher in *28/*28 individuals (6% compared to 1% heterozygotes and 2% wild-type). Conclusions: Patients homozygous for the UGT1A1*28 allele are at significantly increased risk of developing serious adverse events. Despite the clear relationship between UGT1A1 polymorphisms and sacituzumab-govitecan toxicity, the review suggests that there is insufficient consensus on the need for systematic genetic screening. However, the findings indicate that such screening could be useful for identifying patients at risk and personalizing sacituzumab govitecan therapy.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-03-25
2025
2025-03-25
dc.type.none.fl_str_mv review article
http://purl.org/coar/resource_type/c_dcae04bc
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/25203
url https://hdl.handle.net/20.500.13003/25203
dc.language.none.fl_str_mv Español
spa
language_invalid_str_mv Español
language spa
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/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-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
_version_ 1869404433458135040
score 15,811543

Similares en LA Referencia