The association between location of BRCA mutation and efficacy of PARP inhibitor as a frontline maintenance therapy in advanced epithelial ovarian cancer: a multicenter real-world study in South Korea

Abstract

The location of BRCA mutations may influence sensitivity to PARP inhibitors. This study evaluated progression-free survival (PFS) benefit from PARP inhibitors in newly diagnosed ovarian cancer based on BRCA1/2 mutation location. Among 380 patients with BRCA1 (63.7%) or BRCA2 (36.1%) mutations, those with DNA binding domain (DBD) mutations showed significant PFS benefit (BRCA1: HR, 0.34; BRCA2: HR, 0.25; p=0.01). In contrast, BRCA1 BRCT domain mutations showed no significant benefit (HR, 0.76; p=0.44). PFS benefit was observed in both OCCR (HR, 0.49) and non-OCCR (HR, 0.51) groups (p<0.01). These findings suggest that frontline PARP inhibitors provide significant PFS benefit, particularly for patients with DBD mutations, while BRCT domain mutations show limited benefit.