Alés-Martínez, José EnriqueBalmaña, JudithSánchez-Rovira, PedroSalvador Bofill, Francisco JavierGarcía Sáenz, Jose ÁngelPimentel, IsabelMorales, SerafínFernández-Abad, MaríaLahuerta Martínez, AinharaFerrer, NeusZamora, PilarBermejo, BegoñaDíaz-Redondo, TamaraLópez-Ceballos, María HelenaGalan Gramaje, MariaPérez-Escuredo, JhuditCalabuig, LauraSampayo, MiguelPérez-Garcia, José ManuelCortés, JavierLlombart-Cussac, Antonio2024-10-162024-10-162024-10Alés-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.https://hdl.handle.net/20.500.13003/21121To 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Breast NeoplasmsAgedGenes, BRCA1Germ-Line MutationTrastuzumabAdultHumansBRCA2 ProteinAntineoplastic Combined Chemotherapy ProtocolsMiddle AgedGenes, BRCA2Receptor, ErbB-2PiperazinesFemaleTreatment OutcomeBRCA1 ProteinPhthalazinesresearch articleResultado del TratamientoProteína BRCA1Genes BRCA2Receptor ErbB-2FemeninoProteína BRCA2TrastuzumabPiperazinasHumanosPersona de Mediana EdadProtocolos de Quimioterapia Combinada AntineoplásicaAncianoFtalazinasMutación de Línea GerminalNeoplasias de la MamaAdultoGenes BRCA1PhthalazinesPiperazinesTrastuzumabBreast NeoplasmsGerm-Line MutationAntineoplastic Combined Chemotherapy ProtocolsReceptor, ErbB-2HumansFemaleMiddle AgedAdultAgedBRCA2 ProteinGenes, BRCA2BRCA1 ProteinGenes, BRCA1Treatment Outcome10.1016/j.breast.2024.1037801532-308039116683L20337327032-s2.0-85200573237001302243000001open access