624 Benefit from maintenance with parp inhibitor in newly diagnosed ovarian cancer according to the mutation type and site

Introduction/Background Little is known about correlations between the type and the location of the BRCA1/2 mutations and the magnitude of response to Poly (ADP-ribose) polymerase inhibitors (PARPi) in advanced ovarian cancer (OC), as maintenance. Methodology This retrospective study enrolled patients with newly diagnosed BRCA-mutated high-grade serous or endometrioid OC who received PARPi maintenance alone after first-line chemotherapy. Progression-free survival (PFS), as the time interval between the last cycle of platinum and the date of subsequent progression or last follow-up, was compared according to the location in the functional domains of BRCA1 Really Interesting Gene (RING), DNA-binding domain (DBD), or BRCA1 C-terminal domain (BRCT) and BRCA2 RAD51-binding domain (RAD51); DBD. Besides, survival analysis based on the mutation type (frameshift, missense, nonsense and splicing) was performed. Results 140 patients who underwent PARPi as first-line maintenance were compared with 128 patients who did not receive PARPi in the same setting. Among them, 62.3% harbored BRCA1m and 37.3% BRCA2m. After a median follow-up of 33 months, benefit from maintenance with PARPi was observed irrespective of the location of BRCAm. Notably, patients with BRCA1m located in the RING and BRCT domains showed the most significant benefit, with 24-month PFS not reached (NR) (PARPi) in both groups, compared with 11 months in No-PARPi -RING arm Hazard ratio HR8.62 (1.00–74.81) and 13 months in No-PARPi-BRCT arm HR7.82 (1.65–37.15)). In BRCA2m patients, 24-month PFS rates were 39.1% (No-PARPi) and 83.2% (PARPi) in cases of mutations in the RAD51[HR 4.13 (1.66–10.29). With regard to mutation type, the greatest effect of PARPi was obtained in the missense mutation group, with 24-month PFS NR (PARPi) vs17 months (No-PARPi), respectively HR 14.25 (1.85–109.71). Conclusion First-line maintenance with PARPi in BRCA-mutated OC patients demonstrated PFS benefit, regardless of mutation location and type, particularly in the RING, BRCT (for BRCA1), RAD51 domains (for BRCA2) and missense mutation. Disclosures None.