53P Description of BRCA mutated high-grade ovarian cancer demonstrating primary resistance to first-line platinum in the French national multicenter ESME database

High-grade epithelial ovarian cancer (HGOC) harboring a BRCA mutation (BRCAm) are the proof of concept for a homologous recombination deficient tumor. As a result of this defect in a crucial DNA repair pathway, most BRCAm OC are sensitive to first-line platinum-based chemotherapy. However, a small subset of patients (pts) with BRCAm OC demonstrate primary chemo-resistance. We aimed to describe the prevalence, clinico-pathological characteristics, and disease evolution of pts with primary resistant/refractory BRCAm OC (PROC). We conducted a retrospective observational cohort study based on OC data from the Epidemiological Strategy and Medical Economics (ESME) platform which centralizes real-life data of pts aged ≥ 18 years treated for OC in France between 2011 and 2022. PROC was defined as pts who received non-platinum chemotherapy in second-line for progression. Out of the 13,032 pts included in the ESME database, 1505 pts with BRCAm HGOC were identified. The prevalence of PROC among pts with BRCAm OC was 3.3% (43/1302). When comparing BRCAm PROC and BRCAm platinum sensitive OC (PSOC) pts, there were no significant differences in age at diagnosis (p=0.1798), but there was a trend in distribution of BRCA1(77 vs 66%) vs BRCA2 (21 vs 34%) mutations (p=0.0687). BRCAm PROC was more frequently associated with non-serous histology (29% vs 16%, p=0.042), with higher FIGO stage at diagnosis (85% vs 41% stage IV, p=0.0003), and non-operable disease at diagnosis (77% vs 55%, p= 0.004). Pts with BRCAm PROC had higher ca125 values at diagnosis and at last platinum than PSOC patients (mean 3364 vs 2090, p=0.04, and 562 vs 51U/mL, p<0.0001, respectively). Median PFS and OS were 10.2 7.6-11.7 and 29.2 months 19.0-43.2 respectively in BRCAm PROC pts, and 34.0 31.9-36.8 and 95.1 months 88.0-104.9 in PSOC pts. PROC is rare among pts with BRCAm OC but their prognosis is catastrophic. BRCAm PROC pts were more likely to have non-serous histology and exhibited more advanced disease at diagnosis than PSOC pts. We did not identify any other predominant features distinguishing PROC pts. These results suggest the importance of early cancer screening in BRCAm pts.