Benefit from maintenance with PARP inhibitor in newly diagnosed ovarian cancer according to BRCA1/2 mutation type and site: a multicenter real-world study

作者：Cristina Marchetti, Anna Fagotti, Robert Fruscio, Chiara Cassani, Lorena Incorvaia, M T Perri, Carolina Maria Sassu, Cristina Angela Camnasio, Emilia Giudice, Angelo Minucci, Marta Seca, Eloisa Arbustini, Laura Vertechy, Maria De Bonis, S M Boccia, Diana Giannarelli, Vanda Salutari, Mariagrazia Distefano, Maria Gabriella Ferrandina, Camilla Nero, Lucia Musacchio, Antonio Russo, Giovanni Scambia, D. Lorusso · 发表于：ESMO Open · 年份：2025 · DOI：10.1016/j.esmoop.2025.104533 · 被引用次数：17 · 研究领域：PARP inhibition in cancer therapy、BRCA gene mutations in cancer、Ovarian cancer diagnosis and treatment

BACKGROUND: Knowledge about the association between the BRCA1/2 mutation type and location and response to poly (ADP-ribose) polymerase inhibitors (PARPis) as single agent in ovarian cancer is limited. This study aimed to investigate the effectiveness of PARPi based on functional domains (FD) [RING, BRCT, DNA-binding (BD), RAD51-BD] and types (frameshift, missense, nonsense, splicing) of BRCA1/2 gene mutations in ovarian cancer. MATERIALS AND METHODS: This multicenter real-world study retrospectively enrolled BRCA1/2-mutated ovarian cancer patients receiving olaparib maintenance between January 2010 and December 2022. Data were compared with historical series of patients who did not receive olaparib and analyzed based on the FD involved in BRCA1/2 mutations. Progression-free survival was calculated from the date of the last platinum-based treatment until recurrence or last follow-up. RESULTS: After a median follow-up of 46 months (range 32-60 months), 140 patients who underwent olaparib maintenance were compared with 128 who did not. PARPi showed efficacy in the overall population. The no-exon 11 patients benefitted more from olaparib than exon 11 patients [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.25-0.93]. In the BRCA1 group, patients with mutations in RING and BRCT domains had significant benefits from PARPi (HR 0.08, 95% CI 0.01-0.75; HR 0.10, 95% CI 0.02-0.38, respectively). Among BRCA2-mutated patients, RAD51-BD mutations were associated with higher respons...