Homologous recombination deficiency score for predicting efficacy of platinum-based chemotherapy and PARPi maintenance therapy in ovarian cancer.

person Jinhua Wang Jiangsu cancer hospital, Nanjing, Jiangsu, China info_outline Jinhua Wang, Jing Shen, Zhe Zhang, Lei Ye, Jin Lu, Ziyi Xiao, Lihua Zhang, Xiaojian Liu, Chan Zhu, Xiaoxuan Wang, Chao Zhang, Xing Zhang, Dong-sheng Chen, Xinyu Xu

Authors person Jinhua Wang Jiangsu cancer hospital, Nanjing, Jiangsu, China info_outline Jinhua Wang, Jing Shen, Zhe Zhang, Lei Ye, Jin Lu, Ziyi Xiao, Lihua Zhang, Xiaojian Liu, Chan Zhu, Xiaoxuan Wang, Chao Zhang, Xing Zhang, Dong-sheng Chen, Xinyu Xu Organizations Jiangsu cancer hospital, Nanjing, Jiangsu, China, Huai'an Second People's Hospital, Huai'an, China, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, Jiangsu, China, Jiangsu Cancer Hospital, Nanjing, China, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, China, Jiangsu simcere diagnostics Co,.Ltd, Nanjing, Jiangsu, China, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China Abstract Disclosures Research Funding No funding sources reported Background: Currently, homologous recombination deficiency (HRD) has been confirmed to be a predictive biomarker for poly-ADP-ribose-polymerase inhibitors (PARPi) in ovarian cancer, while its effects on the clinical outcomes of platinum-based chemotherapy and PARPi maintenance therapy are not assessed rigorously in ovarian cancer. We developed an HRD assay to evaluate the effect of HRD scores on the platinum-based chemotherapy and PARPi maintenance therapy in Chinese patients with ovarian cancer. Methods: HRD testing was performed on the samples obtained at primary cytoreductive surgery. The progression-free survival (PFS) was observed among the BRCA -mutated/HRD-positive and BRCA wild-type/HRD-negative patients. Univariate and multivariate COX analyses were performed to test the association of PFS with different variables, and hazards ratios (HR) and 95% confidence interval (CI) were calculated. The two-tailed p value less than 0.05 was considered statistically significant. Results: Totally 74 patients who received platinum-based chemotherapy were eligible for the study, among whom 81.1% responded to the initial platinum-based chemotherapy, 33.8% harbored BRCA1/2 mutations and 74.3% were HRD-positive. The median HRD score of platinum-sensitive patients (n=60) was 48.5, significantly higher than the 31 of platinum-resistant patients (n=14, p =0.0035). Analysis of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale state transitions (LST) between platinum-sensitive and platinum-resistant patients showed significant differences in TAI ( p =0.0012) and LST ( p =0.004). Compared with HRD-negative patients, HRD-positive patients had a significantly longer median PFS (10 vs . 15 months, p =0.017), and multivariate analysis further indicated that HRD-positive status (HR, 0.423, 95%CI: 0.191-0.939, p =0.035) was a significant predictor for the improvement of PFS. Conclusions: The HRD assay developed in our study can accurately predict the response to platinum-based chemotherapy and PARPi efficacy in patients with ovarian cancer, providing powerful evidence for implementation of genetic testing and guidance of clinical treatment in ovarian cancer.