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

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). OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged ≥18 years diagnosed with HER...

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Detalhes bibliográficos
Autores: Alés-Martínez, José Enrique, Balmaña, Judith, Sánchez-Rovira, Pedro, Salvador Bofill, Francisco Javier, García Sáenz, Jose Ángel, Pimentel, Isabel, Morales, Serafín, Fernández-Abad, María, Lahuerta Martínez, Ainhara, Ferrer, Neus, Zamora, Pilar, Bermejo, Begoña, Díaz-Redondo, Tamara, López-Ceballos, María Helena, Galan Gramaje, Maria, Pérez-Escuredo, Jhudit, Calabuig, Laura, Sampayo, Miguel, Pérez-Garcia, José Manuel, Cortés, Javier, Llombart-Cussac, Antonio
Tipo de documento: artigo
Data de publicação:2024
País:España
Recursos:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositório:Docusalut
Idioma:inglês
OAI Identifier:oai:docusalut.com:20.500.13003/21121
Acesso em linha:https://hdl.handle.net/20.500.13003/21121
Access Level:Acceso aberto
Palavra-chave:Breast Neoplasms
Aged
Genes, BRCA1
Germ-Line Mutation
Trastuzumab
Adult
Humans
BRCA2 Protein
Antineoplastic Combined Chemotherapy Protocols
Middle Aged
Genes, BRCA2
Receptor, ErbB-2
Piperazines
Female
Treatment Outcome
BRCA1 Protein
Phthalazines
Resultado del Tratamiento
Proteína BRCA1
Genes BRCA2
Receptor ErbB-2
Femenino
Proteína BRCA2
Piperazinas
Humanos
Persona de Mediana Edad
Protocolos de Quimioterapia Combinada Antineoplásica
Anciano
Ftalazinas
Mutación de Línea Germinal
Neoplasias de la Mama
Adulto
Genes BRCA1
Descrição
Resumo: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). 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 investigator-assessed 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. 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. This study suggests that the combination of olaparib plus trastuzumab may be effective and safe in pre-treated patients with HER2-positive gBRCAm 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.

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