Homologous recombination deficiency (HRD) status and response to platinum-based chemotherapy and PARP inhibitors in Chinese patients with ovarian cancer.

Abstract

e17533 Background: The association between platinum-based chemotherapy and PARPis response and HRD status in Chinese epithelial ovarian cancer patients has not been fully elucidated. Methods: We assessed homologous recombination deficiency (HRD) score using genomic scar analysis (GSA) algorithm of Beijing Genomics Institute (BGI) assay. The definitive HRD status were determined by combining HRD score tested with the BGI assay and homologous recombination repair (HRR) gene mutation status. We then tested the association of HRD with response to platinum-based chemotherapy and PARP inhibitors in Chinese patients with ovarian cancer. Results: In total, 209 patients with definitive HRD status were included: 66.0% (138 of 209) for HRD and 34.0% (71 of 209) for non-HRD. Patients with HRD tumors were more likely to have a larger tumor (73.9% vs 59.2%, P = 0.029), and less likely to receive neoadjuvant chemotherapy (48.6% vs 67.6%, P = 0.009). No differences were found between patients with HRD and non-HRD tumors in age at diagnosis, histology, stage, postoperative residual disease status. In the entire cohort, patients with HRD tumors were more likely to be platinum sensitive with a platinum-free interval (PFI) of > 6 months than those with non-HRD (79.6% vs 65.7%, P=0.030). Patients with HRD had a significantly better PFS and OS than patients with non-HRD in the entire study population (PFS: unadjusted HR = 0.54, 95% CI: 0.38–0.77, P = 0.001; and OS: unadjusted HR = 0.44, 95% CI: 0.26–0.75, P = 0.002). Multivariate analysis showed that patients with HRD was an independent predictor of increased PFS and OS (PFS: HR = 0.56, 95% CI: 0.39-0.82, P = 0.002; OS: HR = 0.50, 95% CI: 0.29-0.86, P = 0.012). In patients who received PARPis as first-line maintenance (n=55), the median duration of PARPis was 23.3 months (1.2-40.0 months) and 11.0 months (1.4-39.1 months) in HRD and non-HRD subgroup, respectively. Patients with HRD had a significantly better PFS than non-HRD patients (median PFS: NR vs 22.5 months, unadjusted HR = 0.39, 95% CI: 0.16-0.97, P = 0.035). Multivariate analysis showed that patients with HRD was an independent predictor of increased PFS (HR = 0.22, 95% CI: 0.07-0.68, P = 0.008). Conclusions: Patients with HRD tumors are more likely to respond to platinum-based chemotherapy and PARPis when compared with those who are non-HRD. HRD tumors associate with a better survival in Chinese ovarian cancer patient.