RT Journal Article
T1 Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study
A1 Alés-Martínez, José Enrique
A1 Balmaña, Judith
A1 Sánchez-Rovira, Pedro
A1 Salvador Bofill, Francisco Javier
A1 García Sáenz, Jose Ángel
A1 Pimentel, Isabel
A1 Morales, Serafín
A1 Fernández-Abad, María
A1 Lahuerta Martínez, Ainhara
A1 Ferrer, Neus
A1 Zamora, Pilar
A1 Bermejo, Begoña
A1 Díaz-Redondo, Tamara
A1 López-Ceballos, María Helena
A1 Galan Gramaje, Maria
A1 Pérez-Escuredo, Jhudit
A1 Calabuig, Laura
A1 Sampayo, Miguel
A1 Pérez-Garcia, José Manuel
A1 Cortés, Javier
A1 Llombart-Cussac, Antonio
AB 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.
PB Elsevier
YR 2024
FD 2024-10
LK https://hdl.handle.net/20.500.13003/21121
UL https://hdl.handle.net/20.500.13003/21121
LA eng
NO Alés-Martínez JE, Balmaña J, Sánchez-Rovira P, Salvador Bofill FJ, García Sáenz JÁ, Pimentel I, et al. Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study. Breast. 2024 Aug 2;77:103780.
DS Docusalut
RD 27 sept. 2026