HRD as a predictor of response to platinum-based chemotherapy and PARP inhibitors in a Chinese ovarian cancer population.

Abstract

e17571 Background: Homologous Recombination Deficiency (HRD) predicts response to platinum-based chemotherapy and PARP inhibitors (PARPi) in ovarian cancer. This real-world study aimed to evaluate the value of HRD status, accessed via a genomic scar analysis (GSA) algorithm, and platinum sensitivity, PARPi efficacy in Chinese epithelial ovarian cancer (EOC) patients. Methods: We retrospectively analyzed 209 non-mucinous EOC patients treated at our hospital between Jan 2016, and Jun 2021. The HRD score was calculated by GSA algorithm (BGI Genomics). HRD positivity was defined as pathogenic BRCA1/2 mutations and/or an HRD score≥30; other patients were seemed as homologous recombination proficient (HRP). Associations with platinum response, progression-free survival (PFS), and overall survival (OS) were assessed using Kaplan-Meier and Cox regression. Results: Of 209 patients, 62.2% were HRD and 37.8% were HRP, with a median follow-up of 67.9 months (range: 3.6-99.9). The median PFS for the entire cohort was 22.3 months, which was longer in the HRD group than in the HRP group (30.0 vs. 15.4 months; P=0.003). At the final follow-up, 36.8% of patients had died. The median OS was longer in the HRD group (not reached vs. 47.4 months; P=0.001). In multivariate analysis, HRD was an independent predictor of both longer PFS (HR=0.64, 95% CI: 0.45-0.90; P=0.010) and OS (HR=0.46, 95% CI: 0.29-0.73; P=0.001). Platinum-sensitive relapse rate was higher in the HRD group (79.8% vs. 66.7%; P=0.034). Among HRD patients, those with BRCA mutations (BRCAmt) had superior PFS (HR=0.62, 95% CI: 0.40-0.95; P=0.028) and OS (HR=0.52, 95% CI: 0.28-0.98; P=0.042) versus BRCA wild-type (BRCAwt). In the subset receiving first-line platinum-based chemotherapy without PARPi maintenance (n=147), the median PFS and OS were 16.7 and 80.3 months, respectively. HRD remained associated with improved PFS (22.2 vs. 13.7 months; P=0.007) and OS (not reached vs. 44.2 months; P=0.002). Multivariate analysis confirmed HRD as an independent predictor for longer PFS (HR=0.64, 95% CI: 0.44-0.94; P=0.022) and OS (HR=0.45, 95% CI: 0.27-0.76; P=0.003). Within this HRD subgroup, BRCAmt patients had longer OS (HR=0.46, 95% CI: 0.22-0.95; P=0.037) and a trend toward longer PFS (HR=0.66, 95% CI: 0.41-1.07; P=0.091) versus BRCAwt patients. Among patients receiving first-line PARPi maintenance therapy (n=60), the median PFS was 76.3 months. OS data were not yet mature. HRD patients had longer PFS than HRP patients (not reached vs. 22.5 months; P=0.034), with HRD status independently predicts prolonged PFS in multivariate analysis (HR=0.41, 95% CI: 0.18-0.95; P=0.037). Conclusions: HRD status by GSA is a valid predictor of response to platinum-based chemotherapy and PARPi therapy in Chinese patients with EOC and is associated with improved survival. Within the HRD group, BRCAmt patients have a more favorable prognosis.