51P Efficacy of PARP inhibitors in patients with advanced high grade serous ovarian cancer according to BRCA domain mutations
نویسندگان
چکیده
Poly ADP-ribose polymerase inhibitors (PARPi) have revolutionized the treatment of high grade serous ovarian carcinoma (HGSOC), especially those harbouring BRCA1/2 mutations. Emerging preclinical evidence suggest a potential relationship between BRCA specific-domain defects and sensitivity to PARPi. In particular, ring-less BRCA1 protein, characterized by residual activity in RAD51 foci formation, has been associated with reduced response On contrary, mutations (mut) BRCA2 DNA binding domain (BD), that is essential for RAD51-induced architectural rearrangement BRCA2, an increased Real world data regarding PARPi efficacy according specific mut are missing. The clinical pts advanced HGSOC BRCA1/2mut who received first-line platinum-based chemotherapy followed from 2018-2021 at University Naples Federico II were retrospectively collected. classified location protein (DNA-BD, BRCT, RING finger domain, others) RAD51-BD, others). log-rank test was used assess difference progression-free survival (PFS) distribution groups. Among 41 pts, 25 harboured BRCA1mut (61%) 16 BRCA2mut (39%). DNA-BD BRCT detected 3 (12%), 8 (32%), 7 (28%) respectively; other (28%). RAD51-BD (50%) 6 (38%) 2 (13%). No statistical differences terms PFS observed (P = 0.87) or 0.18) domains. Interestingly, numerically longer median BD compared defects, (log-rank trend P 0.05). Pts diagnosed derived similar benefit regardless locations BRCAmut. Although limited small cohort size our analysis suggests may predict
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Abbreviations: PARP: Poly(Adp-Ribose) Polymerase; SSBS: Single Strand Breaks; DSBS: Double Strand Breaks; BER: Base Excision Repair; NER: Nucleic Acid Excision Repair; MMR: Mismatch Repair; HR: Homologous Recombination; NHEJ: Non-Homologous End Joining; DNA-PKCS: DNA-Dependent Protein Kinase; ORR: Objective Response Rate; PFS: Progression-Free Survival; PLD: Pegylated Liposomal Doxorubicin; OS:...
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ژورنال
عنوان ژورنال: ESMO open
سال: 2023
ISSN: ['2059-7029']
DOI: https://doi.org/10.1016/j.esmoop.2023.100831