Homologous Recombination Deficiency Associated With Response to Poly (ADP-ribose) Polymerase Inhibitors in Ovarian Cancer Patients: The First Real-World Evidence From China

Abstract

Homologous recombination deficiency (HRD) is an approved predictive biomarker for Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. However, the proportion of positive HRD in the real world and the relationship between HRD status and PARPi in Chinese ovarian cancer patients remain unknown. A total of 67 ovarian cancer patients who underwent PARPi, either olaparib or niraparib, were enrolled and passed inclusion criteria from August 2018 to January 2021 in the Affiliated Cancer Hospital of Nanjing Medical University. HRD status correlation with Progression-free survival (PFS) was analyzed and summarized with a log-rank test. Univariate and multiple cox-regression analyses were conducted to investigate all correlated clinical factors. Approximately 68.7% (46/67) patients were HRD positive and the rest 31.3% (21/67) were HRD negative. The PFS among HRD-positive patients was significantly longer than those HRD-negative patients (medium PFS 9.4 m vs 4.1 m, hazard ratio [HR]: 0.52, 95% CI: [0.38–0.71], p <0.001). Univariate cox-regression found that HRD status, Eastern Cooperative Oncology Group (ECOG) status, BRCA status, previous treatment lines, secondary cytoreductive surgery and R0 resection were significantly associated with PFS after PARPi treatment. After multiple regression correction, HRD status and ECOG were the independent factors to predict PFS (HR: 0.67, 95% CI: [0.49–0.92], p = 0.01; HR: 2.20, 95% CI: [1.14–4.23], p = 0.02, respectively). In platinum sensitivity evaluable subgroup (N = 49), HRD status and platinum sensitivity status remain significant to predict PFS after multiple regression correction (HR: 0.71, 95% CI: [0.51–0.98], p = 0.04; HR: 0.49, 95% CI: [0.24–1.0], p = 0.05, respectively). This is the first real-world study of HRD status in ovarian cancer patients in China, and we demonstrate that HRD is an independent predictive biomarker for PARP inhibitors treatment in Chinese ovarian cancer patients.