Real-world outcomes of maintenance olaparib in homologous recombination deficient, BRCA-negative, high-grade ovarian cancer: Insights from clinical practice in Russia.

Abstract

e17576 Background: Currently there are no clinical data of efficacy of maintenance olaparib in patients with homologous recombination deficiency (HRD)-positive, BRCA-negative, newly diagnosed ovarian cancer (OC) especially with the use of alternative HRD-assay. This retrospective cohort study evaluated the efficacy of maintenance olaparib in patients with BRCA-negative newly diagnosed stage III-IV OC and positive HRD-score determined by AmoyDx panel. Methods: Eligible patients were aged ≥18 years, with histologically confirmed high grade serous or endometrioid OC, stage III-IV, BRCA-negative (by NGS-testing) and positive HRD-test (GSS>50). HRD status was assessed using the AmoyDx panel. Patients were stratified by olaparib maintenance therapy (yes vs. no), genomic signature (high GSS: ≥85; low GSS: 50-84), and clinical risk (low: complete upfront surgery for stage III; high: other criteria).The primary outcomes were progression-free survival (PFS) and overall survival (OS), with additional analysis of the impact of clinical risk factors and genomic signature groups (GSS). Results: From January 2022 to September 2024, 67 patients received maintenance olaparib and 130 patients received bevacizumab or no maintenance therapy across four major oncology centers in Moscow. After a median follow-up of 25 months, the median PFS (mPFS) in the olaparib group was not reached, compared to 16 months in the control group (HR = 0.39, 95% CI [0.25–0.63], p < 0.001). Cumulative PFS rates were 84% in the olaparib group vs. 92% in the control group at 1 year, 64% vs. 46% at 2 years. No significant differences in OS were observed between the groups: 55 months in the olaparib group vs. 52 months in the control group (p = 0.38). In the high GSS subgroup, the mPFS with olaparib was not reached, compared to 17 months in the control group (HR = 0.31, 95% CI [0.16–0.70], p < 0.001). In the low GSS subgroup, the mPFS was 21 months with olaparib vs. 14 months without (p = 0.13). In the high-risk group, the mPFS was 29 months with olaparib vs. 15 months without (HR = 0.49, 95% CI [0.28–0.72], p = 0.015). In the low-risk group, the mPFS was not reached with olaparib, compared to 33 months in the control group (HR = 0.41, 95% CI [0.26–0.62], p = 0.002). The mPFS2 was significantly shorter in the olaparib group: 4 months vs. 9 months in the control group (Breslow, p = 0.021). Conclusions: These results demonstrate the feasibility of using the AmoyDx panel in real clinical practice. Maintenance olaparib significantly improved PFS, consistent with findings from the PAOLA-1 trial, with the greatest benefits observed in patients with high GSS. Statistically significant improvements in PFS were also seen in both high- and low-risk subgroups. The shorter PFS2 in the olaparib group may explain the lack of OS benefit, warranting further investigation.