Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study

Purpose: To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm). Methods: OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged >= 18 y...

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Autores: Alés-Martínez JE, Balmaña J, Sánchez-Rovira P, Salvador Bofill FJ, García Sáenz JÁ, Pimentel I, Morales S, Fernández-Abad M, Lahuerta Martínez A, Ferrer N, Zamora P, Bermejo B, Díaz-Redondo T, López-Ceballos MH, Galán M, Pérez-Escuredo J, Calabuig L, Sampayo M, Pérez-Garcia JM, Cortés J, Llombart-Cussac A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p19066
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/19066
Access Level:acceso abierto
Palabra clave:HER2-Positive
Advanced breast cancer
BRCA mutation
Olaparib
Trastuzumab
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spelling Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 studyAlés-Martínez JEBalmaña JSánchez-Rovira PSalvador Bofill FJGarcía Sáenz JÁPimentel IMorales SFernández-Abad MLahuerta Martínez AFerrer NZamora PBermejo BDíaz-Redondo TLópez-Ceballos MHGalán MPérez-Escuredo JCalabuig LSampayo MPérez-Garcia JMCortés JLlombart-Cussac AHER2-PositiveAdvanced breast cancerBRCA mutationOlaparibTrastuzumabPurpose: To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm). Methods: OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged >= 18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in BRCA1 or BRCA2 who had received at least one prior systemic regimen for advanced disease were enrolled. Patients received olaparib plus trastuzumab until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was investigatorassessed clinical benefit rate for at least 24 weeks as per RECIST v.1.1. Key secondary endpoints included overall response rate (ORR) and safety profile. Results: A total of 68 pre-treated HER2-positive ABC patients were screened. Due to slow accrual the trial was stopped after enrolling 5 patients instead of the planned sample size of 20. Four patients achieved clinical benefit (80.0 %, 95 % CI; 28.4-99.5, p <0.001) and the primary endpoint was met. The ORR was 60.0 % (95 % CI; 14.7-94.7), including one complete response. Four (80.0 %) patients experienced at least one treatment-related treatment-emergent adverse event (TEAE). Most TEAEs were grade 1 or 2. There were no treatment-related deaths and no new safety signals were identified. Conclusions: This study suggests that the combination of olaparib plus trastuzumab may be effective and safe in pre-treated patients with HER2-positive g BRCA m ABC. This ABC patient population should be further studied and not be pre-emptively excluded from clinical trials of targeted therapy for BRCA1/2-driven cancers.CHURCHILL LIVINGSTONE2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/19066BREASTISSN: 09609776ISSNe: 15323080reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p190662026-06-07T16:35:31Z
dc.title.none.fl_str_mv Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study
title Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study
spellingShingle Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study
Alés-Martínez JE
HER2-Positive
Advanced breast cancer
BRCA mutation
Olaparib
Trastuzumab
title_short Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study
title_full Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study
title_fullStr Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study
title_full_unstemmed Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study
title_sort Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study
dc.creator.none.fl_str_mv Alés-Martínez JE
Balmaña J
Sánchez-Rovira P
Salvador Bofill FJ
García Sáenz JÁ
Pimentel I
Morales S
Fernández-Abad M
Lahuerta Martínez A
Ferrer N
Zamora P
Bermejo B
Díaz-Redondo T
López-Ceballos MH
Galán M
Pérez-Escuredo J
Calabuig L
Sampayo M
Pérez-Garcia JM
Cortés J
Llombart-Cussac A
author Alés-Martínez JE
author_facet Alés-Martínez JE
Balmaña J
Sánchez-Rovira P
Salvador Bofill FJ
García Sáenz JÁ
Pimentel I
Morales S
Fernández-Abad M
Lahuerta Martínez A
Ferrer N
Zamora P
Bermejo B
Díaz-Redondo T
López-Ceballos MH
Galán M
Pérez-Escuredo J
Calabuig L
Sampayo M
Pérez-Garcia JM
Cortés J
Llombart-Cussac A
author_role author
author2 Balmaña J
Sánchez-Rovira P
Salvador Bofill FJ
García Sáenz JÁ
Pimentel I
Morales S
Fernández-Abad M
Lahuerta Martínez A
Ferrer N
Zamora P
Bermejo B
Díaz-Redondo T
López-Ceballos MH
Galán M
Pérez-Escuredo J
Calabuig L
Sampayo M
Pérez-Garcia JM
Cortés J
Llombart-Cussac A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HER2-Positive
Advanced breast cancer
BRCA mutation
Olaparib
Trastuzumab
topic HER2-Positive
Advanced breast cancer
BRCA mutation
Olaparib
Trastuzumab
description Purpose: To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm). Methods: OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged >= 18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in BRCA1 or BRCA2 who had received at least one prior systemic regimen for advanced disease were enrolled. Patients received olaparib plus trastuzumab until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was investigatorassessed clinical benefit rate for at least 24 weeks as per RECIST v.1.1. Key secondary endpoints included overall response rate (ORR) and safety profile. Results: A total of 68 pre-treated HER2-positive ABC patients were screened. Due to slow accrual the trial was stopped after enrolling 5 patients instead of the planned sample size of 20. Four patients achieved clinical benefit (80.0 %, 95 % CI; 28.4-99.5, p <0.001) and the primary endpoint was met. The ORR was 60.0 % (95 % CI; 14.7-94.7), including one complete response. Four (80.0 %) patients experienced at least one treatment-related treatment-emergent adverse event (TEAE). Most TEAEs were grade 1 or 2. There were no treatment-related deaths and no new safety signals were identified. Conclusions: This study suggests that the combination of olaparib plus trastuzumab may be effective and safe in pre-treated patients with HER2-positive g BRCA m ABC. This ABC patient population should be further studied and not be pre-emptively excluded from clinical trials of targeted therapy for BRCA1/2-driven cancers.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/19066
url https://incliva.portalinvestigacion.com/publicaciones/19066
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv CHURCHILL LIVINGSTONE
publisher.none.fl_str_mv CHURCHILL LIVINGSTONE
dc.source.none.fl_str_mv BREAST
ISSN: 09609776
ISSNe: 15323080
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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