Abstract PS2-04-29: Parp inhibitors use in patients in germline palb2 or somatic brca1/2 mutations carriers with metastatic breast cancer: real life data from the esme database

Abstract Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) are approved for the treatment of HER2-negative metastatic breast cancer (MBC) in germline (g)BRCA1/2 pathogenic alteration (m) carriers. Olaparib and talazoparib showed efficacy in MBC patients with somatic (s)BRCA1/2m and/or gPALB2m in phase 2 trials. We aimed to investigate the effectiveness of PARPi in this setting in the real-life ESME cohort. Methods: ESME-MBC, a nationwide observational cohort, gathers data on MBC patients treated in 18 French Cancer Centers from 2008 on. We selected all patients treated with PARPi and who had either sBRCA1/2m or gPALB2m MBC. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) from treatment initiation, PFS and OS according to type of mutation, type of PARPi and line of treatment. The Kaplan-Meier method was used to assess survival. Results: Among 35,687 patients included in the ESME database from 2008 to 2022, 57 were eligible for the present analysis (46 with sBRCA1/2m;11 gPALB2m). Median age at treatment was 54 years [31-83]). 39% were triple negative MBC (17 sBRCA1/2m and 5 gPALB2m), 60% HR-positive/HER2-negative (28 sBRCA1/2m and 6 gPALB2m). The median number of treatment lines prior PARPi, including endocrinotherapy, was two [0-9]. PARPi was initiated in first- or second line for 24 patients, representing 64% of triple-negative patients and 42% of HR-positive/HER2-negative patients. 32 patients (56%) received olaparib, 22 talazoparib (39%, all with sBRCA1/2m) and 3 another PARPi. A clinical trial was the context for 36.8% of prescriptions. In the whole population, median PFS and OS were 5.4 [95%CI: 4.3; 8.3] and 13.2 months [11.2; 19.7] respectively. For patients bearing sBRCA1/2m and gPALB2m, median PFS were 4.9 [3.0; 8.2] and 8.3 [3.0; not achieved (NA)] months respectively, and median OS 12.1 [10.4; 19.7] and 17.6 [2.4; NA] months respectively. Median PFS was 4.9 [2.8; 6.7] and 8.2 months [3.9; 13.1] for talazoparib and olaparib respectively; and median OS 12.1 [7.2; 24.3] and 15.0 months [10.1; 26.6]. Conclusion: In this multicenter real-life cohort of MBC patients with a sBRCA1/2 or a gPALB2 mutation, effectiveness of PARPi appeared in line with phase II trials. These data further support the use of olaparib or talazoparib in gPALB2m, and possibly in sBRCA1/2m. Citation Format: P. ROTTIER, L. CHALTIEL, Z. NEVIERE, W. JACOT, A. MAILLIEZ, F. DALENC, T. BACHELOT, E. BRAIN, V. MASSARD, B. SAUTEREY, T. GRINDA, C. BAILLEUX, M. ARDENOS, L. BOSQUET, G. EMILE. Parp inhibitors use in patients in germline palb2 or somatic brca1/2 mutations carriers with metastatic breast cancer: real life data from the esme database [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-04-29.