Comparison of BRCA genetic testing and subsequent treatment with PARP inhibitors (PARPi) for ederly vs non-elderly women with non-mucinous epithelial ovarian cancer (EOC): A large prospective cohort study from the Australian National Gynaecology Oncology Registry (NGOR).

Mahendra Naidoo Monash University School of Public Health and Preventive Medicine - Cancer Research Program, Melbourne, VIC, Australia info_outline Mahendra Naidoo, Clare L. Scott, Orla McNally, Rob Rome, Sharnel Perera, John Raymond Zalcberg

Authors Mahendra Naidoo Monash University School of Public Health and Preventive Medicine - Cancer Research Program, Melbourne, VIC, Australia info_outline Mahendra Naidoo, Clare L. Scott, Orla McNally, Rob Rome, Sharnel Perera, John Raymond Zalcberg Organizations Monash University School of Public Health and Preventive Medicine - Cancer Research Program, Melbourne, VIC, Australia, Peter MacCallum Cancer Centre, Parkville, Australia, The Royal Women's Hospital, Melbourne, Australia, Epworth HealthCare, Melbourne, VIC, Australia, Monash University School of Public Health and Preventive Medicine, Melbourne, VIC, Australia, Monash University School of Public Health and Preventive Medicine and Department of Medical Oncology, Alfred Health, Melbourne, VIC, Australia Abstract Disclosures Research Funding Other Government Agency NHMRC Background: The 5-year survival rate for elderly women (≥ 75 years) with ovarian cancer is 25%. Germline mutations in BRCA1/BRCA2 are identified in approximately 15% of newly diagnosed women with ovarian cancer and have implications for prognosis and predicted benefit of both platinum chemotherapy and PARPi therapy. Objectives: To compare differences in, and subsequent management of Elderly (aged ≥75 years) vs Non-elderly (aged <75 years) women with non-mucinous EOC who underwent germline and somatic BRCA1/BRCA2 testing across the Australian NGOR sites from 2017 – 2022. Methods: Clinical data were sourced from NGOR patient databases and assessed to confirm accuracy prior to analysis. Results: Data on 1579 eligible women between May 2017 and July 2022 across 21 hospitals were collected. Patient characteristics are summarised in Table 1. The rates of germline testing in Elderly women was 51% compared to 71% in Non-elderly women and this difference was statistically significant (p<0.001). The rates of somatic testing in Elderly women was 28% compared to 33% in Non-elderly women although this difference was not statistically significant (p=0.2). In Elderly women with either germline or somatic pathogenic BRCA mutations and Stage III/IV disease, 67% received PARPi within 8 weeks of chemotherapy completion compared to 53% in Non-elderly women. In a multi-variate analysis, the most significant characteristic associated with reduced germline testing was the ‘Elderly’ compared to ‘Non-elderly’ group (OR 0.41, 95% CI: 0.30-0.58, p < 0.001). Germline testing was more likely to be conducted in postcodes associated with higher Socioeconomic status (SES) quintiles 2-5 compared to quintile 1 (OR 2.06, 95% CI: 1.50-2.81, p< 0.001) and in those women receiving operative and chemotherapy treatment compared to chemotherapy alone (OR 1.84, 95% CI: 1.08-3.11, p=0.024). Conclusions: The rates of germline and somatic BRCA testing are lower than anticipated, particularly germline testing in Elderly women. Women known to have pathogenic germline or somatic BRCA mutations may have received PARPi at lower rates than expected. Further studies are required to understand the cause of such variations, including accounting for the advent of government funded BRCA testing, PARPi funding and correlating effects on survival. Patient characteristics. Characteristic Non-Elderly aged <75 (n= 1293 ) Elderly Aged ≥75 ( n = 286 ) p-value Cancer stages 1-2 Cancer stages 3-4 336 (30%) 771 (70%) 47 (20%) 190 (80%) 0.001 ECOG 0-1 ECOG 2 -4 925 (92%) 83 (8.2%) 180 (79%) 49 (21%) <0.001 Serous morphology Other morphology 857 (75%) 281 (25%) 223 (85%) 39 (15%) < 0.001 Cancer grades 1-2 Cancer grade 3 165 (15%) 961 (85%) 24 (9.5%) 228 (90%) <0.032