The impact of homologous recombination deficiency on first-line adjuvant chemotherapy and first-line PARPi maintenance therapy in Chinese patients with epithelial ovarian cancer.

Abstract

e17573 Background: Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Methods: We developed a customized sequencing panel named “Precision Human HRD Assay”.This HRD assay contains two sets of probes, HRD-score probes (~50K) and DDR-gene probes, which were used to evaluate HRD score and genotype 36 DDR genes. Then we applied it to two large Chinese EOC patient cohorts and performed a retrospective analysis of progression-free survival (PFS) and overall survival (OS) estimated using the Kaplan-Meier method. Results: In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526 to 0.899; P = 0.003) and OS (median, 89.5 months vs. 60.9 months; HR, 0.636; 95% CI, 0.423 to 0.955; P = 0.008). In the first-line PARPi maintenance therapy cohort (FPMT, N = 83), HRD status significantly improved PFS (median, NA vs 12 months; HR, 0.438; 95% CI, 0.201 to 0.957; P = 0.033) and OS (median, NA vs NA months; HR, 0.12; 95% CI, 0.029 to 0.505; P = 0.001). Conclusions: Our results demonstrate that HRD status is a significant predictor for PFS and OS in both first-line chemotherapy and first-line PARPi maintenance therapy, providing strong real-world evidence for conducting genetic testing and improving clinical recommendations for Chinese EOC patients.