Association between genomic instability score and progression-free/overall survival in patients with newly diagnosed non-BRCA1/2 ovarian cancer.

Objective: We sought to describe the association between genomic instability score (GIS) and progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed, non-BRCA1/2 ovarian cancer.

Methods: Homologous recombinant deficiency (HRD) status was based on a cutoff of ≥42 GIS; patients <42 were categorized with homologous recombination proficiency (HRP). We collected type and duration of maintenance therapy, among other variables, and built a multivariate model with landmark analysis at 6 months from baseline and applied it for time-dependent variables.

Results: Increasing GIS as a continuous variable was associated with improved PFS and OS in our cohort. Overall, median PFS was significantly longer in patients with HRD ovarian cancer (35.4 months, 25.4-NE) than in those with HRP disease (14.9 months, 13.1-16.2; p < 0.001). Median OS was 36.2 months (32.4-NE) for HRP and not reached for HRD (p = 0.002). Notably, in patients with HRP ovarian cancer, we observed a shorter median PFS in those who received a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) than in those who did not (12.7 months for HRP with PARPi vs 15.2 months for HRP without PARPi).

Conclusions: Our results demonstrate that in newly diagnosed advanced non-BRCA1/2 ovarian cancer, GIS as a continuous variable is associated with longer PFS and OS. In patients with HRP ovarian cancer, PARPi treatment may be associated with shorter PFS, which warrants further evaluation.