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

Authors :
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
Galán, María
Pérez-Escuredo, Jhudit
Calabuig, Laura
Sampayo, Miguel
Pérez-Garcia, José Manuel
Cortés, Javier
Source :
Breast; Oct2024, Vol. 77, pN.PAG-N.PAG, 1p
Publication Year :
2024

Abstract

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 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. • HER2 overexpression in g BRCA m is infrequent. • Olaparib plus trastuzumab showed promising efficacy in patients with HER2-positive ABC and g BRCA m. • This patient population should not be excluded from clinical trials of targeted therapy for BRCA1/2 -driven cancers. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09609776
Volume :
77
Database :
Supplemental Index
Journal :
Breast
Publication Type :
Academic Journal
Accession number :
179557187
Full Text :
https://doi.org/10.1016/j.breast.2024.103780